A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for All the newly synthesized compounds were screened for in vitro α-amylase inhibitory activity at 5, 10, 25, 50, 100, 200, 400, 500µg/ml concentration. Among the synthesized compounds, T1 and T5 showed good percentage of inhibition at all concentration (5 µg/ml-500 µg). The IC50 values for these compounds were found to be 25 µg/ml and 30 µg/ml respectively which are close to IC50 value of acarbose (10 µg/ml). T3 and T4 showed moderate α-amylase inhibitory activity at all concentrations. The IC50 value for these compounds found to be 59 µg/ml and 110 µg/ml respectively. Among the test compounds, compound 2-(4-chlorophenyl)-3-(4, 6- dimethylpyrimidin-2-yl)thiazolidin-4-one (T1) was found to be the most active agent which showed 88.00 µ g/ml α-amylase inhibition in the highest concentration, which have p-chloro phenyl group in the 4-thiazolidinone nucleus.