She won Best Actress at the Montreal World Film Festival in 2001 for her role in Betty Fisher and Other Stories and has been nominated for a César Award three times.

Mathilde Seigner is appreciated for her spontaneity and strong character, she quickly gained favor with the public, thanks to the nostalgic Une hirondelle a fait le printemps (2001) as a city dweller who discovers the joys of the countryside.

She appeared in Le passager de l'été, Zone libre, and Dance avec lui.

She returned in 2009 with three dramatic comedies about family (Quelque chose à te dire, Trésor and Une semaine sur deux (et la moitié des vacances scolaires)).

[citation needed] She is the sister-in-law of film director Roman Polanski, who married her sister Emmanuelle in 1989.