Nathan Lane
Spot Helperman / Scott Leadready II / Scott Manly-Manning (voice)

Kelsey Grammer
Dr. Ivan Krank (voice)

Shaun Fleming
Leonard Amadeus Helperman (voice)

Debra Jo Rupp
Mrs. Mary Lou Moira Angela Darling Helperman (voice)

David Ogden Stiers
Mr. Jolly (voice)

Jerry Stiller
Pretty Boy (voice)

Paul Reubens
Dennis (voice)

Megan Mullally
Adele (voice)

Wallace Shawn
Principal Crosby Strickler (voice)

Rob Paulsen
Ian Wazselewski (voice)

Jay Thomas
Barry Anger (voice)

Estelle Harris
Mrs. Boogin (voice)

Genie Francis
Marsha / Marcia (voice)

Anthony Geary
John / Juan (voice)

Rosalyn Landor
The Blue Fairy (voice)

Pamela Adlon
Trevor / Taylor / Tyler (voice)

Timothy Stack
Father (voice)

Emma Steinkellner
Little Girl (voice)

Ken Swofford
Officer White (voice)

Lauren Tom
Younghee (voice)