Thiazolidinediones, a class of oral insulin sensitizing agents that improve insulin resistance, are agonists of peroxisome proliferator activated receptor-Y (PPAR-y). Two clinically used drugs pioglitazone (ACTOS) and rosiglitazone (AVANDIA) have made a great contribution to therapy for type 2 diabetes. However, weight gain and hepatotoxicity are side effects of thiazolidinediones. For thiazolidinediones with lesser side effects, researchers are focusing on modification of side chain at C-5 of thiazolidinedione nucleus and its derivatization, Netoglitazone possesses both PPAR-α/γ dual agonistic activity. More thiazolidinedione derivatives like DRF-2189, PHT46, PMT13, DRF-2519 can be utilized as potent antidiabetic agents in future.