Villains
Jack Ampersand / Professor Exclamation (voiced by Phil LaMarr) is a punctuation-themed supervillain who has short arms due to losing his elbows in a freak accident and now wants to make the world bend to him.
Lauren/The Destructress and Lyle/FistPuncher (voiced by Alyson Stoner and Brock Powell respectively) are fraternal twins who had an encounter with the same aliens as Hamster and Gretel, granting them similar powers. Unlike the latter, they were told to use their powers for evil, becoming supervillains as a result. Starting with "The Bitter Sitter", Lauren has a second job as a babysitter in order to have a non-evil hustle. However, Lauren later turned over a new leaf in the episode "Evil Upheaval" while Lyle maintains his evil ways. Lyle has attempted twice to get Lauren back on the side of evil.
El Luchador (voiced by Carlos Alazraqui) is a wrestler-themed supervillain who loves ropa vieja.
Rodney Thunderpants (voiced by James Adomian) is a cowboy who has electrokinesis and a deep hatred of cellphones.
Van Dyke (voiced by Casey Hamilton) is a sentient Van Dyke beard who can possess people by attaching himself to their faces. After getting shredded by a lawnmower, he later puts himself back together as a moustache.
Coach Haggerty (voiced by Betsy Sodaro) is a cheerleading coach that hypnotizes people to commit crimes for her using her whistle.
La Cebolla (voiced by Karina La Voz) is a former telenovela star-turned-villainess who encountered the unseen aliens, granting her the ability to communicate with onions and onion-related plants.
CopyCat (voiced by Eric Bauza) is a comic book geek with a huge trust fund and a degree in engineering who invents a super suit based on the comic book character "Man Cat."
Neighslayer (voiced by Thomas Sanders) is a former track star who was mutated into a half-horse half-man mutant after an experiment gone awry. This left him with horse hooves in place of his human arms and legs.
Dr. Eelgood (voiced by Keith Ferguson) is a mad scientist who has sworn revenge on the local aquarium and has genetically engineered a nearly indestructible eel. He was one of Dave's tenants, although he was evicted when his experiments were exposed.
Ideal Eel is an eel-like monster created by Dr. Eelgood. It was destroyed when Gretel froze it solid and Hamster accidentally dropped it.
Bouncy Castle (voiced by Richie Moriarty) is a bouncy castle that was accidentally given life by the aliens who were trying to empower two nearby children. It sought revenge for all the times that people jumped in it. The Bouncy Castle was deflated by Hamster and Gretel.
X-Terminator (voiced by John DiMaggio) is a supervillain who has a vendetta against rodents of all kinds after his human body was accidentally merged with his rat-catching device.
The Amplifier (voiced by Khary Payton) is a supervillain with a ray gun that can dramatically increase the size of whatever it shoots.
The Nightmarionette (voiced by Michael-Leon Wooley) is a villain who can create life-like projections of people's greatest fears.
Bob Infantiburg / Big Baby (voiced by Brock Powell) is a former mayoral candidate and Veronica Hill's ex-boyfriend who accidentally turned himself into a kaiju-sized baby.
Sloppy Joe Monster (vocal effects provided by Dee Bradley Baker) is a sloppy joe monster created from a leftover sloppy joe by the aliens. Its body was destroyed by Gretel and its brain was eaten by Churro.
Tina (voiced by Camryn Grimes) is a new student in Gretel and Bailey's class who turns out to be a spy from the country of Bolgylvania.
The Earworm (voiced by Adam Rose) is a songwriting supervillain whose evil jingle hypnotizes Hamster and Gretel.
Christine DuPoulet / The East Side Bantam (voiced by Cree Summer) is the former chicken-like school mascot that tries to sabotage every school play after being replaced by the East Side Plumber mascot. She was said to have disappeared during the stage production of The Vikings of Venzance, but in reality, she fled due to severe stage fright and hid under the stage while dressed as the East Side Bantam. After being thwarted by Gretel, who also suffered from stage fright, Christine becomes the new mascot of "Frank's Discounted Discount Costumes".
Record Scratch (voiced by Camryn Grimes) is a villain who can take over the world with her DJ skills. It was later revealed that she was just a disguise by the Imposter.
Clovis Jerome Wojtowski / The Imposter (voiced by Diedrich Bader) is a villain who wears multiple disguises.
Ernie (voiced by Brock Powell) is a villainous baker that attacks people with his "divorce cakes" after people refused to buy them.
Belle (voiced by Karalynn Dunton) is a social media influencer who starts a smear campaign against Hamster and Gretel to increase her number of followers.
Arthouse (voiced by Diedrich Bader) is a disgruntled film artist who produces mundane "short" films.
Tchotchke Jones (voiced by Richard Kind) is a tchotchke shop owner, who shrinks historical landmarks and puts them in bottles.
Micromanager (voiced by John Hodgman) is the owner of Small Burger and a former employee of Tall Burger who got fired after he accidentally shrunk himself with a device meant to shrink onions and now wants to literally destroy his competition.
Charlie / Father Goose (voiced by Isaac Robinson-Smith) is a man with goose wings on his rear end who wants to bring about the next step of human evolution by turning the populace into geese.
Helen / Rat Burglar (voiced by Rachel Dratch) is a villain dressed as a rat, who uses "Invisible Ink" on herself to secretly help her son Xavier cheat in contests without getting caught.
Crimson Haste (voiced by Sarah Sherman) is a villainess with supersonic speed, who runs a rapid local delivery service by stealing the goods unnoticed.
Bob Stanley Cashwell / Unknownzy (voiced by Isaac Robinson-Smith) is a masked villain who invested in, and later vandalized, Hiromi's mural.
Stan / Pendulum Pete (voiced by Diedrich Bader) is a villain with grandfather clock pendulums for arms, who has a deep loathing for digital clocks.
Inga the Ice Queen (voiced by Danielle Threet) is a Swiss cryokinetic villainess who owns an ice cream parlor and traps cool people in ice to force them to be her friends.
La Sombrerona (voiced by Joanna Hausmann) is a villainess who wears five hats as a tribute to her five dead husbands, and now strives to strip everyone of their happiness.
Simon (voiced by Brock Powell) is a talking nanobot who has the ability to control people and transform them into cyborgs.
Julie Jennings / Dr. MedusaSaurus (voiced by Lexie Shoaibi) is an uncredited paleontologist who was trapped in a tar pit containing toxic waste for thirty years and was reawakened by the aliens, granting her the ability to reanimate dinosaur skeletons.
Itsy Bitsy (voiced by Tessa Skara) is a villainess who was fused with a spider on her shoulder during an encounter with the aliens, gaining the ability to shoot spider-webs from her underarms.
Bayou Barb (voiced by Jane Lynch) is a former diner employee who was fused to waffle irons and a toxic waste-infused tree, turning into a misunderstood monster and a local bayou legend.
Librarian (voiced by Cree Summer) is the local librarian who wishes to make the city as quiet as her workplace by stealing the populace's voices using a Shush-inator she got from Dr. Doofenshmirtz.
Mary Mitosis (voiced by Debra Wilson) is a villainess with the ability to duplicate herself.
The Flake (voiced by Kyle Mooney) is a villain who gained the ability to turn into flakes after being fused with a croissant.
Clem Clam (voiced by Richard Ayoade) is a man whose head transformed into a clam head after being covered in clam chowder and toxic waste.
Demo Broz (voiced by Joel Armogasto Martinez and Andrew Santiago) - Luis and Jeffrey are twin construction workers who gained the power to levitate objects by high-fiving each other after their encounter with the aliens.
FootKicker (voiced by Seth Green) is an inmate who becomes FistPuncher's new sidekick after a falling out with Destructress. He has an overgrown right foot resulting from a clinical trial, although his super strength is actually in his left foot thanks to the aliens.
ACE (voiced by Carlos Alazraqui) is a robotic crossing guard who goes rogue and declares that humans are unfit to cross the street.
Stress Ball Monster is a monster that was created from Hiromi's stress ball when the female alien felt pity for her. After Hamster threw it into outer space, the aliens took in the Stress Ball Monster.
Connie McBurlap (voiced by Grey DeLisle) is a disgraced fashion designer who has invented a fabric that can control the movements of whoever wears it.
Rosie / Dust Might (voiced by Kimberly Brooks) is a mail carrier and a supervillainess obsessed with antiques who can summon dust clouds and giant mites.
Slamonade Stan (voiced by Bobby Moynihan) is a human-turned-flavored drink bottle who was fired as the Slamonade mascot after a youth focus group disapproved, and now wants revenge on the cool kids.
Hank Franklin (voiced by Lance Krall) is a game show host and influencer with permanent ink on his face, who wants to prank the whole city.
Carl (voiced by Sebastian Conelli) is a man who fused himself with a classic car in hopes of impressing his dismissive father.
Felix Van Schurk (voiced by Brett Gelman) is a scientist that was found in a VHS by Gretel and Bailey after a failed attempt to become electricity and travel to a pizzeria.
The Mud Singer (voiced by Stephen Kramer Glickman) is a mud-themed villain who Kevin fought when he ended up with Gretel's powers.
Mordros the Annihilator (voiced by Alfred Molina) is a notorious planet-destroying villain who the aliens are preparing Hamster and Gretel to fight and who the other alien races fear. The episode "Who's Afraid of Mordros the Annihilator?" reveals that Mordros was originally a chinchilla named Nutmeg with a history with Mrs. Maybank who was transported into space during the 1960s and mutated by cosmic energy. Additionally, his name originated as an acronym for Project M.O.R.D.R.O.S. which is short for Military Office Research Deploying Rodent Orbital Study.
Robot Hamster & Gretel (voiced by Beck Bennett and Meli Povenmire) are robot counterparts of Hamster and Gretel who were created by Mordros the Annihilator to destroy the main duo. The robots were created by combining Hamster and Gretel's DNA with their network and have the same abilities as them.
Robot Kevin (voiced by Michael Cimino) is the robot counterpart of Kevin who was also created by Mordros the Annihilator. Since Mordros was not able to combine Kevin's DNA with the robot's network, he was instead depicted as a trash can. Dave later teaches him to love himself for who he is.
Ludwig Von Shrute / The Conductor (voiced by Tom Kenny) is a symphony conductor villain that creates music-note-shaped laser drones in order to destroy the moon.
Burt (voiced by Chris Diamantopoulos) is a bodybuilder who wants revenge on his old gym, where he was bullied for skipping leg day.