Dog Man is a police officer who has the head of a dog and the body of a man, created after an explosion injured a cop and a police dog. He struggles with focus and impulsivity, often getting distracted by chasing squirrels on his way to work. Despite his canine tendencies causing occasional chaos, he is a kind-hearted protector of the city. He serves as the superhero alter-ego The Bark Knight in the Supa Buddies club.

Li'l Petey is a small striped cat and the clone of the villainous Petey. Unlike his genetic source, Li'l Petey is inherently good-natured and curious. He loves toilet humor and frequently tells ridiculous knock-knock jokes. He forms part of a loving pseudo-family with Dog Man and 80-HD, adopting the superhero alter-ego Cat Kid to help save the day.

Petey is a striped cat and a reformed villain who is currently housed in Cat Jail. He originally cloned himself to achieve criminal greatness but inadvertently created the inherently kind Li'l Petey instead. Petey struggles with irritability and his criminal past, but his profound attachment to Li'l Petey continuously pushes him toward heroism.

80-HD is a nonverbal robot who lives with Dog Man and Li'l Petey. As a creative and highly capable mechanic, he builds incredible inventions like the Dogmobile and hydraulic ramps to help his friends. He expresses his emotions through art and a flip-o-rama mask designed by Li'l Petey, operating as the superhero Lightning Dude.

Piggy is a literal pig and the villainous leader of a group known as The Fleas. Harboring a massive grudge against Petey for getting their childhood Critter Scouts group shut down, he plans elaborate retribution using advanced weaponry. He is aggressive and domineering, frequently expressing frustration over his henchmen's lack of professional villain etiquette.

George is a fifth-grade student who acts as the primary storyteller for the Dog Man comic series. His active imagination and love for making up stories help frame the narrative of the graphic novel. He draws inspiration from assigned school reading to invent wild superhero adventures.

Harold is a fifth-grade student who co-creates the Dog Man comics with his best friend. As an enthusiastic artist, he illustrates the comic series. He uses his artistic skills to bring their outlandish superhero stories and giant mechanical villains to life.

Crunky is a member of the villainous trio The Fleas. He shares a childhood history with Petey in the Critter Scouts and participates in the revenge plot against him. Despite operating as a destructive criminal, he occasionally breaks character to display a surprisingly friendly demeanor toward his enemies.

Bub is the third member of The Fleas, seeking revenge against Petey for the destruction of their childhood scout group. Like Crunky, Bub follows Piggy's lead as they pilot giant mechanical dinosaurs. He sometimes forgets to act like a proper supervillain, easily getting distracted by simple joys like catching fireflies.

Chief is the head of the police force and Dog Man's boss. He is deeply devoted to protecting his city but frequently loses his temper over Dog Man's impulsive, dog-like behavior. Despite his gruff exterior and constant exasperation, he bravely fights criminals on the front lines using whatever unconventional weapons are at hand.

Milly is a dedicated police officer who works alongside Chief. She participates directly in high-stakes pursuits and does not hesitate to use creative, literal methods to fight crime, such as physically bludgeoning villains with heavy encyclopedias.

Sarah Hatoff is a determined journalist who covers the chaotic events in the city. Accompanied by her dog Zuzu, she places herself directly in danger to report on the destructive rampage of The Fleas, prioritizing breaking news over her personal safety.

Zuzu is Sarah Hatoff's loyal canine companion. He accompanies the fearless journalist into highly dangerous situations, including being scooped up by a giant mechanical claw during a citywide rampage.