In 1997, she had begun an acting career in La Nuit du Titanic, played in Paris. In the same year she was chosen by Francis Girod for the film Terminal. In 2000 she co-starred with Isabelle Huppert in Claude Chabrol's Merci pour le chocolat. After appearing in Novo (2002) by Jean Pierre Limosin, she was cast by Roberto Andò for the thriller Sotto falso nome. In 2003, she played in La Maladie de la mort, a film in black and white by first-time Director Asa Mader, which previewed at the Venice Film Festival. In this same year, she co-starred in a Greek film, called Real Life (Alithini Zoi), directed by Panos Koutras. In 2005 she took part in two Italian movies: Romanzo criminale, directed by Michele Placido, and Mare buio, where she was featured alongside Luigi Lo Cascio.

Until 2001 Mouglalis studied at the Conservatoire National Supérieur d'Art Dramatique de Paris (CNSAD) under the direction of Daniel Mesguich. In addition to her native French, she speaks fluent English, Italian, and Spanish, and understands Greek to a limited extent.

Along with her career as an Actress, Mouglalis began a successful modelling career. In 2002 she was chosen by Karl Lagerfeld for the ad campaign for the Amateur Allure de Chanel perfume. He uses her as one of his "muses," promoting Chanel bags, fine jewelry, and watches.

On March 7, 2007, she gave birth to her first child, a daughter named Saul, whom she had with French Director Samuel Benchétrit.

Mouglalis was cast as Coco Chanel in the 2009 film Coco Chanel & Igor Stravinsky, directed by Jan Kounen. The film was chosen to close the 2009 Cannes Film Festival.