John Ritter as Clifford the Big Red Dog (voice)

Wayne Brady as Shackelford (voice)

Grey DeLisle as Emily Elizabeth (voice)

Jenna Elfman as Dorothy (voice)

John Goodman as George Wolfsbottom (voice)

Jess Harnell as Dirk (voice)

Kel Mitchell as T-Bone (voice)

Judge Reinhold as Larry (voice)

Kath Soucie as Jetta / Madison (voice)

Cree Summer as Cleo (voice)

Wilmer Valderrama as Rodrigo (voice)

Earl Boen as Mr. Bleakman (voice)

Cam Clarke as Mr. Mark Howard / Marcus (voice)

Teresa Ganzel as Liza (voice)

Ernie Hudson as P.T. (voice)

Nick Jameson as Sheriff Lewis (voice)

Oren Williams as Charley (voice)