In the present study, an attempt was made to synthesize novel 5-substituted-1,3,4-thiadiazol-2-amines and their Schiff bases to evaluate antioxidant, anti-inflammatory and anticancer activities. Various aromatic acids were made to react with thiosemicarbazide and benzaldehyde conventionally to yield the title compounds. The synthesized compounds were screened for antioxidant and anti-inflammatory activity by DPPH radical and carrageenan induced rat paw oedema model respectively. In silico, in vitro and in vivo anticancer activity was carried out respectively by docking, MTT assay and EAC liquid tumor model. Among the compounds tested, TDZS-4 showed promising antioxidant activity with low IC50 value (16.2 μg/mL). Further, it also exhibited significant reduction in the inflammation both at 1st and 3rd h. Compounds TDZS-1 and TDZS-2 showed better Mol dock scores indicating their better interaction with 2CIB protein. Compounds which showed well docked configuration with 2CIB had also shown better in vitro cytotoxicity on Hep2 cell lines. Among them, treatment of EAC tumor bearing mice with TDZS- 1 was found to be effective. To conclude, Schiff bases showed promising biological activities and the presence of electron withdrawing groupsin the scaffold may assist their activity potential.