Her film breakthrough came with La Fille seule (1995), for which she was nominated for a César Award for Most Promising Actress. Also she received two César Award nominations for Les marmottes (1993) and L'eau froide (1994). Outside France, her best-known role is alongside Leonardo DiCaprio in The Beach (2000). In the fall of 2000, she signed a contract as a spokesmodel with the cosmetics company L'Oréal. She was featured alongside two Models, Laetitia Casta and Noémie Lenoir. She portrayed the character Cosette from the 2000 adaption of Les Misérables.
On 29 September 2001, she gave birth to her first child, a girl named Lila, with production designer Louis Soubrier, whom she met on the set of A Single Girl in 1995. She was in a short-lived marriage with Iain Rogers, a film Director, from 2006 to 2007. From 2007 to 2015, she was in a relationship with actor Arie Elmaleh, whose brother Gad Elmaleh was her co-star in The Valet. Ledoyen and Arie Elmaleh have a son, Isaac, born in July 2010, and a daughter, Amalia, born in April 2014.
In 2013 she was named as a member of the jury at the 70th Venice International Film Festival.
