The escalating crisis of antimicrobial resistance necessitates the exploration of alternative therapeutic agents, with medicinal plants like Phyllanthus niruri offering a promising reservoir of bioactive compounds. This study investigated the phytochemical composition and antibacterial efficacy of aqueous and ethanol extracts of P. niruri against key enteric pathogens: Escherichia coli, Klebsiella sp., and Salmonella typhi. Phytochemical screening revealed a rich profile of secondary metabolites, including alkaloids, flavonoids, tannins, saponins, and terpenes in both extracts. However, the extraction solvent significantly influenced the yield, with the ethanol extract yielding higher concentrations of saponins and flavonoids, while the aqueous extract was richer in terpenes and tannins. The antibacterial activity, evaluated using disc diffusion and broth microdilution assays, was concentration-dependent for all tested bacteria. The ethanol extract demonstrated superior efficacy, with E. coli being the most susceptible (MIC = 15.50 mg/mL), followed by Klebsiella sp. (MIC = 31.35 mg/mL) and S. typhi (MIC = 55.20 mg/mL). The aqueous extract also showed significant, though comparatively lower, activity with a similar susceptibility pattern (E. coli MIC = 15.56 mg/mL; Klebsiella sp. MIC = 30.35 mg/mL; S. typhi MIC = 33.50 mg/mL). The potent antibacterial effect is attributed to the synergistic action of the identified phytochemicals. These findings provide a scientific validation for the traditional use of P. niruri in treating gastrointestinal infections and underscore the influence of the extraction solvent on bioactivity. The results position P. niruri, particularly its ethanol extract, as a compelling candidate for further bioassay-guided fractionation to isolate novel antimicrobial compounds for combating drug-resistant enteric infections.