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
disease states other than type 2 diabetes like neurodegenerative disorders, cancer, spinal cord injury,
asthma, and cardiovascular problems. Furthermore, glitazones, the synthetic thiazolidinediones, also
known as insulin sensitizers, are the largely studied PPARγ agonists and the only ones 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 restrict 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 agonist 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 highlight natural molecules
with potential PPARγ agonistic activity.