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Antibiotic resistance represents a looming public health issue across the globe. Strikingly several medical interventions will increase our vulnerability to infection with antibiotic resistant bacteria. Efforts to minimize fecal–orally transmitted pathogens are inadequate in many developing countries. Present study was designed to access the synergistic potentials of using Nisin a potent bacteriocin, in combination with conventional antibiotics deployed to treat infections caused by enteric gram negative pathogens. The organisms used in the study encompassed multidrug resistant (MDR) E.coli, Enterotoxigenic E.coli (ET) and Shigella Dysenteriae (MTCC 1457).Antibiotic susceptiblity tests confirmed that Ciprofloxacin and Chloramphenicol (30 µg/ml) demonstrated sensitivity to the strains selected. Additionally synergism of Chelating agents (EDTA) with Nisin was also confirmed against the pathogens. Synergistic potential of using Nisin-Chloramphenicol, Nisin-Ciprofloxacin and Nisin-EDTA combinations at their sub MIC concentrations were confirmed by invitro experiments comprising radial diffusion assay, Fractional inhibitory concentrations and time kill assays. Further to substantiate the findings, scanning electron microscopy was performed to analyze ultastructural changes in the cell membrane when drugs were used alone or in conjunction with nisin. The findings revealed marked charges in the outer membrane structure of the pathogens studied. These invitro studies could manifest the potentiality of nisin to significantly revamp the antibacterial potential of conventional antibiotics, and furthermore, validate that antibiotics in combination with nisin have considerable potential for combating drug-resistant pathogens.