Type 2 diabetes mellitus is a complex metabolic disorder and is primarily characterized by insulin resistance or reduced insulin sensitivity, combined with reduced insulin secretion and hyperglycemia. Hyperglycemia should be controlled in a careful manner, otherwise higher morbidity and mortality have been found in the related diseases. Therefore, it is essential to control blood glucose levels during the early stages of the type 2 diabetes mellitus. Now a day, the general treatment prescribed for type 2 diabetes mellitus has been a combination of diet, exercise and current therapeutic agents. Among these current therapeutic agents of type 2 diabetes mellitus, thiazolidine-2,4-diones are increased insulin sensitivity action at different tissues such as adipose, muscle and hepatic tissues via acting on peroxisome proliferator activated receptorgamma (PPAR-γ). Currently, various literature surveys related to thiazolidine-2,4-diones reveal that, various substitution present at the 5-positions of thiazolidine-2,4-diones may be varied. Therefore, the present review article is extensively covered various 5-substituted thiazolidine-2,4-diones and its different actions in co-operation with PPAR-γ. In this article also included detail mode of action of thiazolidine-diones and its binding pockets studies via acting on PPAR-γ