Leleges, Kares , Phoenicians, Dorians and Ionians reached Folegandros at times. Several inscriptions found support the assumption that the inhabitants were probably of Doric origin. In the 5th century BC the island participated in the alliance founded by the Athenians after the end of the Persian wars. In an inscription it is noted that Folegandros as a vassal island in 425 BC paid taxes to the Athenians. As the sources testify on the island Artemis Selasforos and Apollo Prostatirios were worshiped.
After the victory of Philip over the Athenians at Chaeronea in 338 BC, Folegandros with the other Cycladic islands was under the dominance of the Macedonians and the Ptolemies later, the successors of Alexander the Great. During the Roman period it became a place of exile. After the Fourth Crusade in 1204 and the distribution of the Byzantine Empire by the Franks, it was under the rule of the Venetians as art of the Duchy of Naxos, head of which was Marco Sanudo, nephew of the Doge of Venice Enrico Dandolo. In 1269 the Frank knight Likarios took command of the Byzantine fleet and recaptured some islands of the Cyclades, including Folegandros.
In 1307, following the peace treaty between the Byzantines and the Venetians, the island came under the dominance of the Spanish knight Giannoulis Dacoronia. In 1464 Folegandros attributed to the house of Gotsantini (Gozzadini) and remained with them until 1617, when it was permanently occupied by the Ottomans. It had actually passed into their hands by 1566 along with the rest of the Cyclades, and residents had to pay a tribute. According to thesources, in 1664 the island church belonged to the Archdiocese of Sifnos. On nautical charts of that periodit it bears the name Polykandros.
In 1715, Canum Hoxha, head admiral of the Ottoman fleet, in retaliation for the pirates who took refuge on the island, looted the island and took 925 residents as captives. It seems that it was then that Sifnians, Cretans and people who came from other places settled there and as a result the island bounced back.
During the Russian -Turkish war it came into the possession of the Russians (1770-1774) and then returned with the Treaty of Küçük Kaynarcato the rule of the Turks. After the Revolution of 1821, Folegandros was included in 1830 along with the rest of the Cyclades in the limits of the newly established Greek state. During the interwar period and during the dictatorship in Greece (1967-1974) political exiles settled in Folegandros.