Oxadiazole is bioactive class of compounds and its derivatives are used widely in drugs and for the treatment of many diseases like neuro-disorders, muscle disorders etc. In the undertaken research work, a series of S-substituted derivatives of 5-(4-nitrophenyl)-1,3,4-oxadiazole-2-thiol (6a-l) were synthesized in various steps. Organic acid 4-nitrobenzoic acid (1) was successfully converted into ester and consequently into its hydrazide in the presence of hydrazine hydrated and methanol as a solvent. Further, 4-nitrobenzoic acid hydrazide (3) yielded 5-(4-nitrophenyl)-1,3,4-oxadiazole-2-thiol, on treatment with carbon disulfide in the presence of base (KOH) and ethanol. Finally the target compounds (6a-l) were obtained by stirring 5-(4-nitrophenyl)-1,3,4-oxadiazole-2-thiol with different electrophiles (5a-l) in the presence of sodium hydride (NaH) and dimethyl formamide (DMF). All these derivatives along with their parent compounds were characterized by IR, EI-MS and 1H-NMR. All the synthesized compounds were assayed for their antioxidant activities and other biological activities. The compounds were screened against...