<b>Background and Objective:</b> <i>Schleichera oleosa</i> (Sapindaceae) has been reported to be useful in traditional medicine and it has some potential pharmacological activities, such as anticancer, antioxidant and antimicrobial activities. This study aimed to assess its safety to provide complete data required for the development of <i>S. oleosa</i> as herbal medicine. <b>Materials and Methods:</b> The safety assessment of the extract was carried out by testing acute and subchronic toxicity in mice (male and female) and rats (male and female), respectively. The doses used in the acute toxicity test were 1000, 2000, 3000, 4000 and 5000 mg kg<sup>1</sup> of body weight and those in the subchronic treatment were 100, 200 and 400 mg kg<sup>1</sup> of body weight. <b>Results:</b> In the acute toxicity test, the <i>S. oleosa</i> leaf extract at all doses indicated that the LD<sub>50</sub> value of the extract was higher than 5000 mg kg<sup>1</sup> b.wt., which suggested that this extract is practically non-toxic according to the toxicity criteria. Furthermore, the subchronic toxicity test found that the administration of the extract to male and female rats at a daily dose of 100 and 200 mg kg<sup>1</sup> b.wt., for 90 days did not cause any significant change in blood haematology, blood biochemistry and histopathological picture of liver, kidney, heart, lymph and lung. Despite there being a significant increase in white blood counts, long-term use of the <i>S. oleosa</i> leaf extract is relatively safe. <b>Conclusion:</b> The results provided evidence regarding the potential of <i>S. oleosa</i> leaves to be used as herbal medicine. However, further research needs to be done to verify that activity and its safety in long-term use.