During the Peloponnesian war; 431 - 404 B.C. the Kalymnians allied with the Athenians. During the war they were invaded by the Spartan admiral Astyocho, who did not however manage
to install an oligarchic command faithful to Sparta and so Kalymnos soon returned to the Athenian alliance. Ιn 333 B.C. after the fall of Halicarnassus to Alexander the Great's generals (Ptolomeus, and Asantros) Kalymnos, like the surrounding islands, was delivered from the Halicarnassus domination. The Greek cities were declared independent states and became allies of Alexander the Great in his war against the Persians.