He was a freedman of the Emperor Hadrian, on whose favorite Antinous he is said to have written a panegyric, specifically called a Citharoedic Hymn (Suidas). Two epigrams by him in the Greek Anthology (Anthol. pal. xiv. 63, xvi. 323) are extant, and a hymn to Nemesis that begins "Nemesis, winged balancer of life, dark-faced goddess, daughter of Justice". The hymn is one of four which preserve the ancient musical notation written over the text. Two other hymns, one to the muse Calliope and one entitled Hymn to the Sun, formerly assigned to Dionysius of Alexandria, have also been attributed to Mesomedes. In an article published in 2003, Annie Bélis proves that the Berlin musical papyrus (inv. 6870) contains a Paean to Apollo written by Mesomedes. A total of 15 poems by Mesomedes are known.
Mesomedes continued in the Musaeum in Alexandria even after Hadrian's death (138); there the Historia Augusta reports that during Antoninus Pius' reign, 138-161 his state salary was reduced. The emperor Caracalla 212-217 honored Mesomedes with a cenotaph approximately a 50-60 years after his death.
Prior to the discovery of the Seikilos epitaph in the late 19th century, the hymns of Mesomedes were the only surviving written music from the ancient world. Three were published by Vincenzo Galilei in his Dialogo della musica antica e della moderna (Florence, 1581), during a period of intense investigation into music of the ancient Greeks. These hymns had been preserved through the Byzantine tradition, and were presented to Vincenzo by Girolamo Mei.
See J. F. Bellermann, Die Hymnen des Dionysius und Mesomedes 1840); C. de Jan, Musici scriptores graeci (1899); S. Reinach in Revue des études grecques, ix (1896); Suidas, s.v.