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The church was built in the 8th century during the Byzantine Papacy over the remains of the Templum Herculis Pompeiani in the Forum Boarium and of the Statio annonae, one of the food distribution centres of ancient Rome (another is to be found at theatre of Balbus). A deaconry was a place where charity distributions were given to the poor, and it looks likely that such an institution would have been built near the Roman annona.

Since it was located near many Byzantine structures, in 7th century this church was called de Schola Graeca, and a close street is still called della Greca. Greek monks escaping iconoclastic persecutions decorated the church around 782, when pope Adrian I promoted its reconstruction; the church was built with a nave and two aisles and a portico. Because of its beauty, the church received the adjective cosmedin (from Greek kosmidion), ornate. A sacristy and an oratory dedicated to St. Nicholas were added in the 9th century, by order of Pope Nicholas I, who also built a papal residence, but they were removed in 1085 by Robert Guiscard's Norman troops. It was in Santa Maria in Cosmedin that Popes Gelasius II (who had been Cardinal Deacon of Titulus S. Mariae in Cosmedin), Celestine III, and Antipope Benedict XIII (Cardinal Deacon of this church) were elected.
A substantial restoration was accomplished in 1118–1124 under Alfanus, camerarius of Pope Callixtus II. After being acquired by Benedictines and a period of decay, in 1718 the church was brought up to a Baroque style, mainly expressed by a new façade, by Giuseppe Sardi in 1718. The Baroque additions, however, were removed in the restoration of 1894–1899 together with the coat-of-arms of Pope Clement XI.

Among the former titular cardinal deacons of the church was Reginald Pole, the last Roman Catholic Archbishop of Canterbury.
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source: wikipedia