Acting as the general administrator of the Comédie-Française between August 2006 and July 2014, Muriel Mayette-Holtz has also worked as both an actress and a director. She attended the classes of Michel Bouquet, Claude Régy and Bernard Dort, and taught at the Conservatoire national supérieur d’art dramatique (National Conservatory of Dramatic Arts of Paris) between 2000 and 2006.

Subsequent to her training at the National Conservatory of Dramatic Arts, she joined the Comédie-Française in 1985 and was appointed as its 477th sociétaire in 1988.
Muriel Mayette-Holtz has performed numerous roles, most notably under the direction of Antoine Vitez in Roja’s La Celestina (1989), of Claude Régy in Sartre’s Behind Closed Doors (1990), of Jacques Lassalle in Marivaux’s The False Servant, (1991), in Molière’s George Dandin, or Confused Husband (1992), and in Chekhov’s Platonov or Fatherlessness (2003), of Matthias Langhoff in Strindberg’s The Dance of Death (1996), and in Büchner’s Lenz, Leonce and Lena (2002).
She has also been directed by Alain Françon in Chekhov’s The Cherry Orchard (1998), by Philippe Adrien in Genet’s The Maids (1997), by Catherine Hiegel in Molière’s Les Femmes savantes and in Pinter’s The Homecoming (2000), by Claude Stratz in Molière’s The Imaginary Invalid (2001) and in Pirandello’s Les Grelots du fou (Cap and Bells, 2005).

During the 2007/2008 season, she performed at the Comédie-Française and on tour Molière’s The Imaginary Invalid staged by Claude Stratz and La Fontaine’s Les Fables put on stage by Robert Wilson. At the Théâtre national de l’Odéon, she staged, in 1990, Oh, mais où est la tête de Victor Hugo? At the Théâtre du Vieux-Colombier, she directed in 1993 Crommelynck’s Les Amants puérils, in 1998 Feydeau’s Chat en poche, in 2001 Karin Mainwaring’s The Rain Dancers, and Marivaux’s La Dispute in 2009. At the Studio-Théâtre, she staged Shakespeare’s The Winter Tale in 2004 and Thomas Bernhard’s Dramalettes in 2005. At the Salle Richelieu, she directed Corneille’s Clitandre in 1996, Bernard Marie-Koltès’ Return to the Desert in 2007, L’Hommage à Molière in 2008, Dario Fo’s Mistero Buffo, and Jean Racine’s Andromache in 2010. Her staging of Bérénice toured during the 2010/2011 season.

Outside the realm of the Comédie-Française, she has played roles in The Misanthrope staged by André Engel, in Gogol’s L’Inspecteur général (The government Inspector), in Heiner Müller’s Quartet and in Garcia Lorca’s Dona Rosita (Doña Rosita The Spinster), all three plays put on stage by Matthias Langhoff, and in La Leçon de M. Pantalone, along with Mario Gonzalez, staged by Christophe Patty (on tour in 2006).
She was conferred the title of a Chevalier (knight) in the Order of Arts and Letters and in the National Order of Merit and a Chevalier (knight) in the National Order of the Legion of Honour.