Microbial infections and antibiotic resistance are some of the prime factors that are ascribed to endanger human health. Several reports have highlighted that drug-resistant pathogens assist in the etiology of various chronic diseases and lead to fatality. The present study deciphered the role of zinc oxide nanoparticles (ZnO NPs) as therapeutics against selected bacterial strains. The plant-based technique was followed to synthesize ZnO NPs. The synthesis was confirmed with different techniques viz. X-ray diffraction, transmission electron microscope (interplanar spacing at 0.126 nm), scanning electron microscope (flower-like structure), and Fourier transform infrared spectroscopy. The antibacterial analysis revealed that ZnO NPs inhibited the growth of all tested strains (Escherichia coli, Staphylococcus aureus, Salmonella typhi, Bacillus subtilis, and Klebsiella pneumoniae) to a greater extent (MIC ranged between 0.013±0.004-0.0625±0 mg/mL) as compared with ZnO compound (Bulk material). In the present study, ZnO NPs were produced in a cost-effective and environmentally sustainable way using a green process and can be used as a remedy for drug-resistant pathogens.