The first inhabitants of Kythnos are the ancient Dryopes with their king Kythnos hence the name of the island also named and Dryopis or Ofiousa. In the Middle Ages was called Thiramna (like Daniel Thiramnios 1661), while the Nile Doxapatri from 1143 mentions the name Thermia, from the hot springs that exist. Later the Turks called "Steam Adasi" (island Baths). And finally the Italians called it "Fermina". O Maroulas, on the northeast coast of the island, near the Loutra, was the oldest establishment of the Cyclades. Excavations brought relics circular structures, which probably were used as places of residence, and few burials.

In ancient times also in Kythnos had established a thriving colony of Ionic Kestoras and Kelifo. The ancient Kythnos occupied in shipping in the Persian wars. The ancient city of Kythnos famous for Eunomia of where and for this reason Aristotle devotes a special study on Kythnos in his work "On Kythnos State" project was not preserved. Also the ancient Kythnos excelled in literature and the arts they highlighted two renowned painters in Timanthi and Kydia.

During Roman times, Kythnos, like the other islands of the Cyclades, declined and sometimes serves as a place of exile and sometimes as a base for pirates.