The intense research interests have been observed in establishing PPAR gamma as a therapeutic target for diabetes. However, PPARγ is also emerging as an important therapeutic target for varied diseased states other than type2 diabetes like neurodegenerative disorders, cancer, spinal cord injury, asthma, and cardiovascular problems. Furthermore, glistazones, the synthetic thiazolidinediones, also known as insulin sensitizers are the largely studied PPARγ agonist and the only one approved for the treatment of type 2 diabetes. However, they are loaded with side effects like fluid retention, obesity, hepatic failure, bone fractures and cardiac failure; which restricted their clinical application. Medicinal plants used traditionally are the sources of bioactive compounds to be used for the development of successful drugs and many structurally diverse natural molecules are already established as PPARγ agonists. These natural partial agonists when compared to full agonists synthetic thiazolidinediones led to weaker PPARγ activation with lesser side effects but are not thoroughly investigated. Their thorough characterization and elucidation of mechanistic activity might prove beneficial for counteracting diseases by modulating PPARγ activity through dietary changes. We aim to review the therapeutic significance of PPARγ for ailments other than diabetes and to highlight natural molecules with potential PPARγ agonistic activity.