The island was first settled in 1131, when Venetian merchant Pietro Gattilesso funded the construction of the church of San Clemente[2] and a hospice for pilgrims and soldiers destined for the Holy Land.

After experiencing a slow decline in the course of the 14th century, San Clemente gained fresh life in 1432, when Pope Eugene IV moved the order of Lateran canons - also known as the Charity (Carità) - to the island.

In 1643, to fulfil a vow made during the plague epidemic that struck the city in 1630, Venetians funded the building of a new chapel, modelled on the Holy House of Loreto, inside the San Clemente church.

The Venetian nobility provided them with financial assistance to restore the church and monastery, and expand the island to add additional houses to the complex.

This female asylum housed women of Venice who were considered insane, earning a reputation amongst Venetians who in time equated 'going to San Clemente' with going mad, much in the way 'Bedlam' has been referred to within England.

Writing of Venice in 1493, Marino Sanudo described the Bucentaur as “a marvel, in which the Prince and Senate go to any great lord visiting the city; they go to San Clemente or elsewhere, depending on the direction from which the visitor is coming”.