Cuando Los Pitufos son perseguidos por Gargamel acaban en Central Park (Estados Unidos), allí deberán buscar la forma de volver a su mundo.
 | Sofía Vergara | Odile |
| Neil Patrick Harris | Johan |
| Katy Perry | Smurfette |
| Jayma Mays | Grace |
 | Alan Cumming | Gutsy Smurf |
| Anton Yelchin | Clumsy Smurf |
 | Hank Azaria | Gargamel |
| B.J. Novak | Baker Smurf |
| Paul Reubens | Jokey Smurf |
| George Lopez | Grouchy Smurf |
| Kenan Thompson | Greedy Smurf |
| Fred Armisen | Brainy Smurf |
| Jonathan Winters | Papa Smurf |
| John Oliver | Vanity Smurf |
| Gary Basaraba | Hefty Smurf |
| Jeff Foxworthy | Handy Smurf |
| Tim Gunn | Henri |
| Wolfgang Puck | Chef Smurf |
