The Theme of Mylasa and Melanoudion (Greek: θέμα Μυλά[σ]σης και Μελανουδίου) was a Byzantine province (thema) in southwestern Asia Minor (modern Turkey) in the 12th and 13th centuries.
The coast however belonged to the Cibyrrhaeot Theme and, after the latter's disbandment sometime during the reign of Manuel I Komnenos (r. 1143–1180), it was joined with the nearby islands of the Dodecanese, chiefly Kos.
Some of the doukes of Mylasa and Melanoudion however seem to have exercised authority over the coast and the offshore islands as well.
The region remained in Byzantine control until conquered by the Turks during the early reign of Andronikos II Palaiologos (r. 1282–1328).
It is notable for the number of Byzantine fortifications which survive there, as well as for the thriving monastic community at Mount Latros.