To generate a new class of scaffolds with amended anti-microbial potency, synthesis and in vitro biological evaluation of a series of 2-((5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)methylthio)-5-substitutedphenyl-1,3,4-oxadiazole (5a-5o) having S-Methylene linkage between the two 1,3,4-diisoxazole rings is reported. Anti-microbial properties of the entire compounds were investigated in a broad panel of some selected gram-positive bacterial strains, gram-negative bacterial strain, and fungal strains using the broth microdilution method. The results were dominant on –Cl and –NO2 functionality than the used standard drug.