Aim: The schistosomicidal activity of Clerodendrum umbellatum leaves aqueous extract (CuAE) has been previously demonstrated. The present study was performed to establish the acute and sub-chronic oral toxicity profile of CuAE in mice. Methods: For acute oral toxicity study, CuAE was administered per os to female mice at a single dose of 2,000 mg/kg. Animals were observed for 14 days in order to identify the signs of toxicity or death. In the repeated dose 28-day oral toxicity study, the extract was administered daily and per os to female and male mice at doses of 200, 400, and 800 mg/kg for 28 consecutive days. A satellite group was also set up. Body weight was measured weekly. Hematological, biochemical, and histopathological parameters were analyzed. Results: CuAE at 2,000 mg/kg produced no sign of toxicity or mortality. In the sub-chronic toxicity study, no mortality, no significant change in the body weight, the relative organ weights, and the hematological parameters were recorded in all treated mice. CuAE at 400 mg/kg significantly increased transaminases activities in male mice. Except for creatinine and high-density lipoprotein-cholesterol in which concentrations are increased after administration of CuAE at 800 mg/kg, the levels of others biochemical markers didn't change. Histopathological abnormalities found in the kidneys were reversible. Conclusion: These results indicated that the LD 50 of CuAE is greater than 2,000 mg/kg and CuAE, therefore, belongs to the category five of relatively non-toxic substances. From the sub-chronic toxicity study, the no-observed-adverse-effect level of CuAE for both male and female mice was considered to be 200 mg/kg/day.