A new series of 2, 5-disubstituted-mercapto-1,3,4-oxadiazole derivatives were synthesized in good yield by reacting different coumarin hydrazide with carbon disulfide & further reacting with various aryl halides. The reactions were monitored by TLC & all derivatives were purified by recrystallization using suitable solvents. The synthesized derivatives were characterized by IR,1H-NMR, Mass spectral data. Further these derivatives were studied for their in-vitro GSK-3? inhibitory activity by using Kinase-Glo Plus luminescence kinase assay & percentage inhibitions were calculated. The standard compound used was CHIR-99021. Some of the derivatives have shown significant in-vitro activity.