Abstract: A quantitative structure activity relationship (QSAR) study on a series of analogs of 5-aryl thiazolidine-2, 4-diones with activity on PPAR-α and PPAR-γ was made using combination of various thermodynamic, electronic and spatial descriptors. Several statistical regression expressions were obtained using multiple linear regression analysis. The best QSAR model was further validated by leave one out cross validation method. The studied revealed that for dual PPAR-α/γ activity dipole-dipole energy and PMI-Z play significant role and contributed positively for PPAR-γ and PPAR-α activity respectively. Thus, QSAR brings important structural insight to aid the design of dual PPAR-α/γ receptor agonist