- Nat Faxon
- Captain Underpants / Mr. Krupp (voice)
- Jay Gragnani
- Harold
- Ramone Hamilton
- George
- Sean Astin
- Narrator / Mr. Gigglenose (voice)
- Dayci Brookshire
- Jessica / Dressy (voice)
- Clancy Brown
- Mr. Ree
- Jorge Diaz
- Melvin / Stanley Peet / Melvin's Dad (voice)
- Peter Hastings
- Comic Narrator
- Evan Kishiyama
- Steve 'Gooch' Yamaguchi
- David Koechner
- Mr. Meaner
- Erica Luttrell
- Erica / George's Mom (voice)
- Patty Mattson
- Miss Anthrope / Harold's Mom (voice)
- Brennan Murray
- Bo Hweemuth
- Kevin Michael Richardson
- Diddlysaurus / George's Dad (voice)
- Mindy Sterling
- Melvin's Mom
- Stephen Tobolowsky
- Creepy Rattlechains
- Kari Wahlgren
- Mayor Hoppy McChapper