Morpholine-2,5-diones are depsipeptide analogues of cyclic dipeptides, derivatives of piperazine-2,5-diones. In contrast to cyclodipeptides, which are formed by spontaneous cyclization, preparation of cyclodidepsipeptides is not easy. Two main ways are used for cyclization of depsipeptides. Cyclization by the formation of ester bond seems more efficient than cyclization via the amide bond formation. The review deals briefly with all known methods of syntheses of morpholine-2,5-diones but attention is also paid to their biological activity. They are of great interest for biomedical applications. Optically active morpholine-2,5-diones are used as monomers for synthesis of biodegradable polymers, as prodrugs of bioactive amino acids and, most recently, in drug delivery systems.