This paper report synthesis and structural characteristic of several analogues of the substituted 2,4-thiazolidinediones. These compounds were evaluated for hypoglycemic activity after oral administration at dose 30mg/kg in alloxan induced diabetic mice. Blood glucose levels were measured and compared with pioglitazone (30mg/kg) as the reference drug. Oral glucose tolerance test (OGTT) was also performed. Quantitative structure activity relationship (QSAR) studies of these substituted 2,4-thiazolidinediones was performed using multiple linear regression analysis.A series of substituted 2,4-thiazolidinediones were synthesized and the structures of synthesized compounds were confirmed by chromatographic and spectral analysis. Compounds 2d, 2e, 2a and 2i have shown significant reduction in Blood glucose level. Improvement in glycemic control was also observed with compounds 2a, 2b, 2c, 2d, 2e and 2i with OGTT. QSAR studies of these substituted 2,4-thiazolidinediones revealed the importance of lipophilic and electronic parameters.