The Basilica of Saints Cosmas and Damian stands on the ruins of the Forum of Peace (also known as the Temple of Peace), commissioned by Vespasian in 71 AD and completed by Domitian. Inaugurated in 75 AD to celebrate the victory in the Jewish War and dedicated to the Pax Augusta, the complex was expanded in the early 4th century by Emperor Maxentius, who erected a temple in honor of his son Valerius Romulus, who died prematurely around 309 AD.

Subsequently, the Ostrogothic king Theodoric the Great and his daughter Amalasuntha donated the temple and the library of the Forum to Pope Felix IV (526-530). The pontiff established the basilica there, dedicating it to Saints Cosmas and Damian, brothers, physicians and martyrs; The choice was intended to contrast their cult with the pagan cult of the Dioscuri (Castor and Pollux), venerated in the nearby temple in the Roman Forum.

Cosmas and Damian, twins born into a noble Arab family, learned the art of medicine in Syria and practiced it in the provinces of Asia Minor. Victims of Diocletian's persecutions, they were martyred in 303 AD. Their profound devotion made the basilica a renowned center for assistance to the needy, so much so that it was initially also known as the Basilica of the Blessed Felicis, after its founder.