After the fall of Constantinople by the Franks, Milos, along with most of the Aegean islands, was conquered by Marco Sanoudos, who founded the Duchy of the sea with Naxos as its capital.

The Sanudis dynasty lasted until 1361. Then, the Sanudis were succeeded by the Krispy Dynasty until 1566. At that time, Milos began to become a stronghold of pirates.

The empire of the Eastern Mediterranean (Venice) is unable to control pirate raids and in 1537 occupies Milos, the famous pirate Hairedin Barbarossa.
At the beginning of the Turkish occupation (1566-1579) Milos was ruled by Joseph Nazis, who was also the last duke of the islands.

Then, all the Cycladic islands pass to the administration of Sultan Murad III. During the years of Ottoman rule, Milos was relatively favored, since the Turks did not live permanently on the island, but only collected taxes through the Commissioners. Turkish rule ended in 1770 with the appearance of the Russians in the Aegean, but after a few years it was restored.