Founded between the 3rd and 4th centuries, it was restored in 1216 by Pope Honorius III (some columns of his building survive in the present building's eastern apse); in 1582; in 1743 designed by Giovanni Battista Nolli and in the 1750s reelaborated by Tommaso De Marchis (his main altar survives); and between 1852 and 1860 by the Somaschi Fathers, who still serve it as a rectory church.

On the south side of the nave is the funerary monument Eleonora Boncompagni Borghese of 1693, to a design of Giovan Contini Batiste, and in the south transept the Chapel of Charles IV of Spain, with the icon Madonna di sant'Alessio, an Edessa icon of the Intercession of the Madonna dating from the 12-13th centuries, thought to have been painted by St Luke the Evangelist and brought from the East by St Alexius.

The crypt's 12th-century wall of frescoes depicts the Agnus Dei and symbols of the Four Evangelists, and on the north aisle St Gerolamo Emiliani introducing orphans to the Virgin by Jean Francois De Troy, and at the end of the aisle The Holy Steps and the titular church of Saint Alexius in wood and stucco by Andrea Bergondi.

The painting has been restored and its subject has been identified by the Italian art historian Claudia Viggiani with Christ the Pilgrim.

[2][3][4] The fresco was firstly discovered in 1965 by the Italian Genio Civile during the stabilization's works of the bell tower, and then discarded for forty years, until 2005.