Nat Faxon
Captain Underpants / Mr. Krupp (voice)
Jorge Diaz
Melvin (voice), Melvin / Melvinborg (voice)
Evan Kishiyama
Steve 'Gooch' Yamaguchi (voice)
Erica Luttrell
Erica / Plungerina (voice), Grace Wain (voice), Erica (voice), Werica Ang (voice)
Laraine Newman
Ms. Ribble (voice), Female Cop (voice), Ms. Ribble / Queen Zombee (voice), Dr. Mentor / Ms. Ribble (voice), Ms. Ribble / Dr. Mentor (voice), Ms. Ribble / Malison Saurus (voice)
David Koechner
Mr. Meaner / Mr. Neamer / Brainy Blabulous (voice), Dr. Will Boryew (voice), Mr. Meaner (voice), Mr. Meaner / Sergeant Boxers (voice), Mr. Meaner / Flabby Flabulous (voice)
Patty Mattson
Miss Anthrope (voice), Miss Anthrope / Clogneta (voice), Miss Anthrope / Chalice Aristocrab (voice)
Clancy Brown
Mr. Ree / Splotch (voice), Mr. Ree (voice)
Eric Bauza
Rap Talkwell (voice), Rap Talkwell / Mr. Gigglenose (voice), Robius (voice)
Kevin Michael Richardson
Diddlysaurus / The Schmoozer (voice), George's Dad / Dune Buggy (voice), Diddlysaurus / Fingers (voice)
Mindy Sterling
Harold's Mom / Melvin's Mom (voice), Melvin's Mom (voice)
Nolan North
Cash Networth / Salamangler (voice), Nanozero / Flash Flood (voice), Cash Networth / Lee Dingman (voice)
Tress MacNeille
Ms. Hurd (voice), Ms. Hurd / DJ Drowsy Drawers (voice)
Maggie Wheeler
Ms. Yewh / TP Mummy (voice), Lunch Lady (voice)
Fred Tatasciore
Keithicus / Rippedicus / Guardicus (voice), Furculees / Chief Hairococha (voice)
Max Koch
Laserlightmare (voice), Hank (voice)
Kari Wahlgren
Mayor Hoppy McChapper (voice)
Stephen Root
Mr. Fyde / Avacadwoe / Hush Muffleman (voice)
Brennan Murray
Bo Hweemuth / Claylossus (voice)
Jim Rash
Señor "Jerry" Citizen (voice)
John DiMaggio
Smelly Socktopus / Suds Latherman (voice)
Rob Riggle
Theodore 'Ted' Murdsly (voice)
Paul Rugg
Vert Ladderfeller III / Altitooth / Bivouac Ladderfeller (voice)
Lewis Black
Ragely J. Snarlingtooth (voice)
Thomas F. Wilson
Major Messy / Camoflush (voice)
Dawn Wells
Gumbalina Toothington (voice)
Toby Huss
Caesar / Cruelius Sneezer (voice)
