Catherine O'Hara as Mrs. Frankenstein / Weird Girl / Gym Teacher (voice)

Martin Short as Mr. Frankenstein / Mr. Burgemeister / Nassor (voice)

Martin Landau as Mr. Rzykruski (voice)

Charlie Tahan as Victor Frankenstein (voice)

Atticus Shaffer as Edgar 'E' Gore (voice)

Winona Ryder as Elsa Van Helsing (voice)

Robert Capron as Bob (voice)

James Hiroyuki Liao as Toshiaki (voice)

Conchata Ferrell as Bob's Mom (voice)

Tom Kenny as New Holland Townsfolk (voice)

Frank Welker as Sparky (voice) (uncredited)

Dee Bradley Baker as Persephone / Shelly / Were-Rat / Colossus / Mr. Whiskers / Driver (voice) (uncredited)

Jeff Bennett as Giant Sea Monkeys (voice) (uncredited)