Herbal products from Paullinia pinnata Linn are widely used in African folk medicine to treat several infectious diseases. Although the extracts from this plant has been shown to possess antimicrobial potential, their activity in infectious diarrhea is less reported. Diarrhea was induced by oral administration of 1.2 × 109 CFU/mL of Shigella flexneri to the rats. The infected rats were treated for 5 days with the doses of 111.42, 222.84, and 445.68 mg/kg of P pinnata. The level of biochemical parameters was assessed and histology of organs examined by 14 days subacute toxicity. S flexneri stool load was considerably reduced after 4 days of treatment with the dose of 445.68 mg/kg, 5 days at the dose of 222.84 mg/kg for the extract, and 2 days with ciprofloxacin. The dose of 111.42 mg/kg appeared efficient after 5 days of treatment. The creatinine level increased at the dose of 445.68 mg/kg in both male and female rats and decrease at the dose of 222.84 mg/mL in female rats while an increase was noted in the male rats. Liver and kidney histology were modified at the dose of 445.68 mg/kg while no change was observed at the doses of 111.42 and 222.84 mg/kg. P pinnata leaf extract is efficient against infectious diarrhea at 111.42 mg/kg without side effect.