She was born Virginie Fernandez in Aubervilliers, Paris, the daughter of Olga, a restaurateur, and Bernard Fernandez, a merchant who sold cleaning products. Her paternal grandfather was Spanish. She was a print model from the age of 2 and later took on the stage name "Ledoyen" after the maiden name of her maternal grandmother, who had been a stage actress.

Her 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 of France, her best-known role is alongside Leonardo DiCaprio in The Beach (2000). In the fall of 2000, she signed a contract with L'Oréal as a spokesmodel with the cosmetics company. She was featured alongside two models, Laetitia Casta and Noémie Lenoir.

On 29 September 2001, she gave birth to her first child, a girl named Lilas. Since July 2010 she has a son Isac with her partner Arie Elmaleh