In this film, released in 2000, she plays the sensual girlfriend of Sergi Lopez, a role for which she earned a nomination for the César for Best Upcoming Female.

She also acted in Gérard Depardieu's Petite Fille and in Jean Becker's film La Tête en friche.

In 2011, Sophie Guillemin went to the other side of the camera and directed her first short film, which she wrote and produced herself: L'Essentiel féminin with Gabrielle Lazure, Shamsy Sharlezya, Cédric Ido and Marie Denarnaud.

It is a burlesque comedy in which a young man strings together disastrous sentimental misadventures until he crosses the gaze of a "mature" woman and understands that the essential is not in appearance, but in inner beauty.

She gave birth to her second child in 2013 and then tried her hand at the experimental film with Philippe Grandrieux in Despite the Night (2014), alongside Ariane Labed and Paul Hamy, then in collaboration with Pascal Luneau, coach of the stars (Marion Cotillard in La Môme, Jérémie Renier in Cloclo, in the film 304 le casting (2015), alongside Jérémy Frérot.

Then she starred in Glacé, an M6 series adapted from Bernard Minier's bestseller where she reunited with Charles Berling 18 years after L'Ennui, and in 2017 'Souviens-toi de nous' for France 2, where she met her future husband, Thierry Godard.

As of January 2024, her most recent film role is that of Martine in Monsieur le maire, directed by Karin Blanc and Michel Tavares.