Big Jim, also known as Commander Cupcake and Snug, is a character who appears in multiple episodes of the Dog Man series. Zorx, Klax, and Jennifer – Three space aliens who planned to invade Piqua, Ohio. They are the main antagonists of the third book. They disguised themselves as lunch ladies to turn the students of Jerome Horwitz Elementary School into Zombie Nerds by using Evil Zombie Nerd Juice. Ms. Tara Ribble – Ms. Ribble is the homeroom teacher of George and Harold's 4th-grade class. In book 5, she is hypnotized into becoming Wedgie Woman. Her name is a pun on the words "terrible" and "miserable." Voiced by Dee Dee Rescher in the movie and Laraine Newman in the TV series. Piggy was originally intended to appear in this book, but never appeared. His return might've been scrapped. Li'l Petey and Molly's songs are parodies based on Twinkle Twinkle Little Star, Take Me Out to the Ball Game, and If You’re Happy and You Know It.

Chief is the leader of the police force and one of the main protagonists, later a supporting character in the Dog Man series. In Mothering Heights, he falls in love with Nurse Lady.Petey's redemption could be based off Krupp's redemption in the Captain Underpants Movie. Where Dav Pilkey himself said that he wished to make Krupp's personality as same as the books when he was still writing then. The primary antagonist of the Dog Man series, Petey, is now a tritagonist. Super Diaper Baby 2: The Invasion of the Potty Snatchers, which was canonized in Dog Man: Mothering Heights, featured him for the first time. Following his string of valiant deeds in Dog Man: Lord of the FLEAS, Petey’s initial status as the series’ primary antagonist was changed. Milligan, Mercedes (June 20, 2018). "DreamWorks 'Epic Tales of Captain Underpants' Opener Undressed". Animation Magazine.

Robo-George and The Harold 2000 – Two giant robots built by Wedgie Woman based on George and Harold. They were fully obedient to Wedgie Woman; each had a vast arsenal of powerful weapons and gadgets and were programmed to destroy Captain Underpants once they heard him say "Tra-la-laaa!" She later appeared in “Dog Man Mothering Heights” in Chief’s dream, as well as later in the book, when she informed Chief that Nurse Lady was on the phone. Mean Officers STATE OF CENSORSHIP: UNABRIDGED CONTRIBUTIONS FROM OUR PARTICIPANTS". National Coalition Against Censorship. Dav Pilkey is an American author and illustrator of children’s literature. He is best known for the Captain Underpants and Dog Man series. Frequently challenged books of the 21st century." American Library Association. Retrieved on October 25, 2013.Wolfe, Jennifer (December 2, 2016). "Rob Letterman Helming Legendary's 'Detective Pikachu' Pokémon Movie". Animation World Network . Retrieved December 25, 2016. HD: In A Tale of Two Kitties, he used 80-HD to retrieve Li'l Petey. In Grime and Punishment, 80-HD breaks three walls and the door of Petey and Son, prompting Petey to make him fix it in the next book. The Tra-La-La Riffic Captain Underpants Collection/The First Captain Underpants Collection (Books 1–4; 1997–2000)