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Nat FaxonCaptain Underpants / Mr. Krupp (voice)
Jay GragnaniHarold (voice)
Ramone HamiltonGeorge (voice)
Sean AstinNarrator / Mr Gigglenose (voice)
Dayci BrookshireJessica / Dressy (voice)
Clancy BrownMr. Ree (voice)
Jorge DiazMelvin / Stanley Peet / Melvin's Dad (voice)
Peter HastingsComic Narrator (voice)
Evan KishiyamaSteve "Gooch" Yamaguchi (voice)
David KoechnerMr. Meaner (voice)
Erica LuttrellErica / George's Mom (voice)
Patty MattsonMiss Anthrope / Harold's Mom (voice)
Brennan MurrayBo Hweemuth (voice)
Kevin Michael RichardsonDiddlysaurus / George's Dad (voice)
Mindy SterlingMelvin's Mom (voice)
Stephen TobolowskyCreepy Rattlechains (voice)
Kari WahlgrenMayor Hoppy McChapper (voice)
