Full of sass and imagination, Pepper Ann follows the daily life of a teenager as she goes to school, hangs out with her friends and has some of the flightiest flights of fancy ever seen in a cartoon. Pepper Ann is a popular adolescent, enthusiastic and opinionated; the girl knows what she likes and she knows what she wants.

Twelve-year old Pepper Ann lives with her divorced mom, Lydia, morose little sister Moose, her environmental activist Aunt Janie, Uncle Jo Jo the cop, and cousin Ned. Pepper Ann's best friend is Milo, a laid-back artist whose name may not be Milo (but he doesn't really care); other students at the school include Nicky Little, a serious violinist, Dieter Liederhosen, a German exchange student, popular and shallow Cissy and twin sisters Tessa and Vanessa, the school's gossip queens. Pepper Ann's world is free of true villains, with the exception of Principal Hickey, who insists on tough discipline, and the snobbish Alice.

Pepper Ann often talks to her mirror reflection which acts as her conscience, guiding during each episode's moral dilemma. The young redhead usually makes the right choice with the help of fantastical scenarios that play out in her head. The show became a hit with audiences for five seasons, both on ABC and Toon Disney.