We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based 1,3,4-oxadiazoles. The synthesized molecules were evaluated for anti-bacterial, anti-fungal and anti-tubercular activities. Promisingly, most of the compounds showed equal or more potency than standard ciprofloxacin against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compound 5e exhibited highest anti-tubercular activity (0.46 μg/mL) close to that of standard Isoniazid (0.40 μg/mL). Equal antifungal activity (1.56 μg/mL) compared to standard Amphotericin-B was shown by most of the compounds. All the N-methylated compounds showed more potent to equal activity against MSSA (MIC 0.39-1.56 μg/mL) and MRSA (MIC 0.78-1.56 μg/mL). All compounds were tested for mammalian cell toxicity using VERO cell line and were found to be non-toxic.