Dog Man is a loyal and determined police officer who combines the fighting skills of a human officer with the keen senses of a dog. He is devoted to fighting crime and keeping the city safe. However, he also retains canine habits that occasionally disrupt police work, such as licking people, rolling in dead fish, and displaying a strong obsession with balls.

Flippy is a butterfly fish who initially exhibits bully-like behavior in a local pet store, attempting to hoard miniature plastic castles and treasure chests. He is purchased as a birthday present for the police chief. After accidentally ingesting brain-enhancing supplements, he gains super-intelligence and telekinetic abilities, giving him the power to carry out villainous plans.

Petey The Cat is an anthropomorphized, orange-and-black striped cat who acts as Dog Man's primary nemesis. He possesses a human-like intellect and frequently devises elaborate criminal schemes involving high-tech inventions like a Love Ray and a Treasure Tank. Despite his intelligence, his plans often fail due to a lack of foresight and unintended consequences.

Flat Petey is a paper cutout created by Petey The Cat to facilitate a jailbreak. Brought to life by a magical spray, he shares his creator's malicious intentions but possesses the physical properties of paper. He quickly establishes his independence and sets out to steal treasure, utilizing a dark sense of humor and a cruel disposition.

The Chief is the loud and excitable head of the police department who struggles with forgetfulness. He genuinely appreciates his team but oscillates between praising Dog Man as his best officer and scolding him for bad behavior. His birthday celebration sets the story's initial events in motion.

Sarah Hatoff is a confident, enthusiastic reporter who documents the city's crime and chaos on her blog. She openly supports the police force and considers herself Dog Man's biggest fan. She frequently carries her newly adopted dog everywhere she goes, inadvertently keeping the small dog close to the action.

Zuzu is a small dog available for purchase at the local pet store. She initially rejects Dog Man's advances but becomes a helpful presence after being adopted by Sarah Hatoff. Because Sarah carries her around, Zuzu is present during major conflicts and uses her canine intuition to communicate important information to the humans.

Dr. Boog E. Feeva is a witch doctor who possesses magical sprays capable of animating inanimate objects and controlling minds. He inadvertently brings Flat Petey to life and quickly becomes the paper villain's unwilling servant after his own mind-control spray is turned against him.

George Beard is an elementary school student who, within the story's fictional universe, serves as one of the authors and creators of the Dog Man comic series. He provides exposition and backstory to catch readers up on the world's rules.

Harold Hutchins is an elementary school student and the in-universe co-creator of the Dog Man comics. Alongside George, he sets the stage for the story's battle between good and evil.

Officer Knight was a human police officer known for his fighting skills and pure heart. After a severe injury caused by Petey The Cat, his body is surgically combined with the head of a police dog, resulting in the creation of Dog Man.

Greg The Dog was an active police canine with keen senses and a loyal brain. Following a fatal explosion, his head is surgically attached to Officer Knight's body, contributing his canine instincts and habits to the new hero, Dog Man.