We report the synthesis and screening of forty novel 4-nitropyrrole-semicarbazide conjugates inspired from the reported bio-potential of bromopyrrole alkaloids and semicarbazide derivatives for antimicrobial activity. Herein, hybrids 5k–5o, 5r, 5s and 5t displayed four-fold increased activity (MIC=0.39μg/mL) against Escherichia coli compared to standard ciprofloxacin. Eight hybrids, 5k–5o and 5r–5t displayed equal antibacterial activity (MIC=1.56μg/mL) against Klebsiella pneumonia compared to standard ciprofloxacin. Hybrid, 5k–5o (MIC=0.195μg/mL) displayed highly potent antibacterial activity against MSSA as compared to standard ciprofloxacin. Eight-fold superior activity was observed for four hybrids 5k–5m and 5o (MIC=0.39μg/mL) against MRSA. Further, nine hybrids displayed four-fold superior antifungal activity (MIC=0.78μg/mL) compared to standard Amphotericin B. Encouraging MICs of these hybrids recognize them as promising leads for development of potential antimicrobial drugs.