Hank Azaria Gargamel Neil Patrick Harris Patrick Winslow Jayma Mays Grace Winslow Sofía Vergara Odile Anjelou Tim Gunn Henri Jonathan Winters Papa Smurf (voice) Katy Perry Smurfette (voice) Anton Yelchin Clumsy Smurf (voice) Madison McKinley Model Meg Phillips Model Mahadeo Shivraj Cabbie Frank Welker Azrael (voice) Mark Doherty Bluetooth Businessman Minglie Chen Young Woman Sean Kenin Guy in Plaid Shirt Victor Pagan Bum Paula Pizzi Odile's Mother Andrew Sellon Waiter Julianna Rigoglioso Little Sister Bradley Gosnell Toy Salesperson Heidi Armbruster Toy Store Parent Skai Jackson Kicking Girl Jojo Gonzalez FAO Custodian Sean Ringgold Inmate Bubba Mario D'Leon Bubba's Inmate Friend Liz Smith Party Guest Tom Colicchio Party Guest Michael Musto Party Guest Joan Rivers Party Guest Olivia Palermo Party Guest Alan Cumming Gutsy Smurf (voice) Fred Armisen Brainy Smurf (voice) George Lopez Grouchy Smurf (voice) Kenan Thompson Greedy Smurf (voice) Jeff Foxworthy Handy Smurf (voice) John Oliver Vanity Smurf (voice) Wolfgang Puck Chef Smurf (voice) Gary Basaraba Hefty Smurf (voice) Paul Reubens Jokey Smurf (voice) B.J. Novak Baker Smurf (voice) Tom Kane Narrator Smurf (voice) John Kassir Crazy Smurf (Voice) Joel McCrary Farmer Smurf (voice) Mary McGloin Mother of Girl in Store (uncredited)