The widespread use of Artabotrys aurantiacus in traditional medicine for the quest for well-being aroused attention for its potential risk to human and animal health. This study points out the acute and sub-chronic toxicological profile of Artabotrys aurantiacus leaves aqueous extract. The extract was prepared following the traditional healer’s method and orally administered to Wistar rats at a single dose of 5000 mg/kg or 50, 100, 200 and 400 mg/kg/day for 45 days for acute and sub-chronic tests, respectively. In acute toxicity, no behavioral disorder was observed in treated animals as compared to the control. The lethal dose of 50 was estimated to be higher than 5000 mg/kg and the extract was noted as slightly toxic. Similarly, no significant change in body weight nor biochemical parameters were observed after 45 days of repeated dosing of the extract. Histological study revealed that all tested doses induced no damage to the liver and kidney as compared to control. These findings indicate that the use of Artabotrys aurantiacus leaves aqueous extract at tested doses is not associated with any toxic effect.