A member of the Socialist Party (PS) since 1982, her career in Montpellier debuted in Georges Frêche's municipal administration.

Frêche gave her important responsibilities such as finances, municipal staff, legal affairs since 1995, and vice-mayor from 2001.

She defeated her UMP opponent Jacques Domergue in a three-way runoff during the 2008 French municipal elections.

Despite being close to Frêche in the past, she has recently distanced herself from him following his notoriously controversial remarks.

On 28 January 2010, following controversial comments made by Frêche about Laurent Fabius, Martine Aubry asked Mandroux to form a list supported by the party for the 2010 regional elections.