Diarrheal disease, characterized by the release of more than three loose or liquid stools per day, remains one of the leading causes of morbidity and mortality in children below 5 years of age in developing countries. Many drugs used in diarrhea management face contraindication and, with regard to infectious diarrhea, resistance of some bacterial strains; this therefore increases the need of new alternative and more effective drugs. This study aimed to evaluate anti-Shigella flexneri activities of Crinum jagus water/ethanol extract. In vitro activities were assayed by disc diffusion and agar dilution methods and in vivo section on Shigella flexneri-induced diarrhea in rats. This was done by oral administration of 9 X 108 CFU of Shigella flexneri to rats that were treated twice daily with Crinum jagus water/ethanol extract for seven consecutive days. Ciprofloxacin was used as positive control. Daily Shigella flexneri load was evaluated. After one treatment week, animals were then sacrificed and interleukins (IL-2 and INF-γ), immunoglobulins (IgA and IgM), motilin, vasoactive intestinal peptide, and ions (sodium, potassium, calcium, and chloride) levels were determined. Also, blood cell count was realized. Crinum jagus water/ethanol extract dose-dependently inhibited Shigella flexneri growth with inhibition diameter of 18.90 and 25.36 mm, respectively, at 0.39 and 200 mg/mL. Minimum inhibitory concentration (MIC) was 0.10 mg/mL and minimum bactericidal concentration (MBC) was 0.30 mg/mL with MBC/MIC ratio of 3.0. In Shigella flexneri-induced diarrheic rats, Crinum jagus reduced (p<0.01) diarrheal stools emission and Shigella load and lowered IL-2, INF-γ, IgA, IgM, and motilin blood levels, whereas it increased (p<0.01) vasoactive intestinal peptide, sodium, potassium, calcium, and chloride blood levels. In diarrheal rats, Crinum jagus restored the decreasing white blood cells and haemoglobin and restored the damaged colon epithelium, where it reduced the density of mucus-filled goblet cells. These results confirm the use of Crinum jagus in ethnomedicine in diarrhea treatment.