Background: The plant Eriosema chinense Vogel (Fabaceae) is mainly found in the Eastern Himalayan regions of India and China, and its roots are used traditionally by the tribal people of Meghalaya (India) in treatment of diarrhea. Objective: The objective of the study was to evaluate the potential of roots from E. chinense against enteropathogenic Escherichia coli (EPEC)-induced infectious diarrhea. Materials and Methods: Ethanolic extract of E. chinense (EEC) roots and its chloroform fraction (CEC) were standardized with eriosematin E using high-performance liquid chromatography. The efficacy of EEC (100 and 200 mg/kg, p.o.) and CEC (50 and 100 mg/kg, p.o.) was evaluated against EPEC-induced infectious diarrhea, where behavioral parameters at the 6th and 24th h followed by determination of water content and density of EPEC in stools along with blood parameters examination. Further, the colonic and small intestinal tissues were subjected to biochemical analysis, antioxidant evaluation, determination of ion concentration, Na+/K+-ATPase activity, and histopathology. Results:The results demonstrated a significant antidiarrheal potential of EEC and CEC at both dose levels; however, EEC at 200 and CEC at 100 mg/kg p.o. were found to be more effective, which also reduced EPEC density in stools and also its water content. The treatment also demonstrated a significant restoration of altered antioxidant and electrolyte status and reactivated Na+/K+-ATPase and prevented epithelial tissue damage. Conclusion: The effect may be attributed to an inhibition in intestinal secretion, nitric oxide production, and reactivation of Na+/K+-ATPase.