Ulcer is a common gastrointestinal disease affecting 5% of the world’s population. Hannoa klaineana is used locally in the management of many gastrointestinal disorders and fevers. The study was conducted to evaluate toxicity profile and anti-ulcer effect of methanol extract of the leaves of Hannoa klaineana (Simaroubaceae). Acute toxicity test was conducted according to OECD guideline 423 using the limit test dose (5000 mg/kg) for 14 days. Sub-chronic toxicity study was carryout according to OECD guideline 407 by daily oral administration of the extract (500 and 1000 mg/kg) for 28 days. Anti-ulcer effect of the extract (100, 200 and 400 mg/kg b.wt) was evaluated using ethanol and indomethacin induced gastric ulcer models. In acute toxicity test, 5000 mg/kg dose of the extract does not caused mortality nor any sign of toxicity observed in the rats, thus, the LD50 value of the extract was above 5000 mg/kg. While sub-chronic toxicity test, the extract demonstrated significant (p<0.01) increase in body weight and weight of the liver, spleen and kidneys of the rats. The result also showed significant (p<0.05) dose-dependent decrease in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid and creatinine. Ethanol-induced ulcer model, the extract demonstrated significant (p<0.05) dose-dependent decrease in mean ulcer index, with percentage inhibition (62.84%) of gastric damage at 400 mg/kg. While indomethacin model, the extract exhibited significant (p<0.001) dosedependent decrease in mean ulcer index with percentage gastroprotection (99.20%) at 400 mg/kg. This study suggested that methanol extract of the leaves of Hannoa klaineana is safe for oral administration and exhibited strong anti-ulcer effect, thus validating the traditional use of the plant leaves in ulcer treatment.