Thiazolidines are multifaceted molecules and exhibit various kinds of biological activities including anticonvulsant and antidepressant activities, chemically thiazolidinediones is a diversified class of heterocyclic nucleus. Thiazolidinediones have shown significant biological activities in various CNS disorder. The mechanism responsible for thiazolidinediones biological activities in CNS based on thiazolidinediones- induced neuroprotection, which is useful in the prevention of microglial activation as well as cytokine expression. The cytokine expression is responsible for inflammatory condition. At the molecular level thiazolidinediones are responsible for the prevention of activation of pro-inflammatory transcription factor as well as promoting the anti-oxidant mechanism in the CNS. In the present article author has elaborated importance of structure activity relationship, molecular mechanism and biological activities with respect to central nervous system. Various investigations suggest that thiazolidinediones may pave the way for the design as well as the discovery of new drug candidates.