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The foundation Pieux Etablissements de la France à Rome et à Lorette is responsible for the five French churches in Rome and apartment buildings in Rome and in Loreto.[2] The foundation is governed by an "administrative deputy" named by the French ambassador to the Holy See.

Giacomo della Porta made the façade as a piece of decorative work entirely independent of the body of the structure, a method much copied later.The French character is evident from the façade itself, which has several statues recalling national history: these include Charlemagne, St. Louis, St. Clothilde and St. Jeanne of Valois. The interior also has frescoes by Charles-Joseph Natoire recounting stories of Saint Louis IX, Saint Denis and Clovis.
Domenichino painted here one of his masterworks, the frescoes portraying the Histories of Saint Cecilia. Other artists who worked in the decoration of San Luigi dei Francesi include Cavalier D'Arpino, Francesco Bassano il Giovanni, Muziano, Giovanni Baglione, Siciolante da Sermoneta, Jacopino del Conte, Tibaldi and Antoine Derizet.

The church's most famous item is, however, the cycle of paintings in the Contarelli Chapel, painted by the Baroque master Caravaggio in 1599-1600 about the life of St. Matthew. This include the three world-renowned canvases of The Calling of St Matthew, The Inspiration of Saint Matthew, The Martyrdom of Saint Matthew.

The church was chosen as the burial place for the higher prelates and members of the French community of Rome: these include the tomb of Pauline de Beaumont, who died of consumption in Rome in 1805, erected by her lover Chateaubriand, the classic liberal economist Frédéric Bastiat, Cardinal François-Joachim de Pierre de Bernis, ambassador in Rome for Louis XV and Louis XVI, and Henri Cleutin the French lieutenant in 16th-century Scotland.