Maison Demandols was built in the early 18th century probably on the design of the famous Baroque architect Romano Carapecchia who came to Malta from Italy in 1707. The architect was involved in other famous projects of the era: the church of St. Catherine of the Langue of Italy, the church of St. Barbara, the church of St. James, and the Manoel Theatre, all in Valletta.
The house was the residence of the Demandols family. The most famous of this family was Bailiff Baldassar de Demandols who was elected as Captain-General of the Navy of the Order of St. John twice in 1650 and 1657. Bailiff Demandols was in command of the 7 galley squadron sent by the Order to assist the Venetians during the Candia (Crete) Campaign against the Ottoman Empire. During this campaign, the Order's squadron managed to capture the galley belonging to Kara Batak Bey of Malvasia off the Venetian island of Tine.