Isatin thiosemicarbazone and its metal complexes have been prepared and structurally characterized by elemental analyses and FT-IR, electronic and 1H-NMR, 13C-NMR spectra. The theoretical wavenumbers, IR intensities, 1HNMR, 13C-NMR spectroscopy, UV absorption spectra and and molecular parameters were calculated by the B3LYP method. Frontier molecular orbital energies, bond length and charges on the atoms of I4NPTH2 and I2-4CPTH2 were studied by the B3LYP method using 6-31G (d,p), 6-311G (d,p), 6-311++G (d,p), 6-311++G (2d,2p)basis sets in gas and DMSO phases. Results showed that compounds 8, 10 and 5 are potent inhibitors of in vitro protein glycation with IC50 value of 111.30 ± 1.96, 113.00 ± 0.9 and 161.51 ± 0.47 μM, respectively While compounds 1- 4 were found to be inactive.