The menace of ravaging infection of trypanosomiases in Africa is of concern in view of the parasites resistance to drug coupled with the cost and extended treatment practice with adverse effect. The prospect of exploiting medicinal plants as alternative in treating illnesses is heightened. This study evaluated the anti-trypanosome activities of the methanol, alkaloid and flavonoid extracts of sarocephalus latifolius leaves. Acute toxicity of the extracts was obtained using the Lorke’s method. In vitro and in vivo analysis of the test plant leaves was determined using different concentrations. The in vitro anti-trypanosome effect of the crude methanol, alkaloid and flavonoid extracts of Sarocephalus latifolius leaf showed that the activity was determined based on dosage with more influence at 4 mg/mL in relation to 0.4 and 0.04 mg/ml. There is significant different (p<0.05) between mice treated with extract and the reference drug. The acute toxicity test was safe as no mortality was recorded at 5000mg/kg of bodyweight of mice. However, in vivo Anti-trypanosome activity of the crude extract at 250 and 500mg/kg bodyweight exposed a trend of increase in the parasite level which was observed when compared with standard control. But, elongation of life in mice was observed. Methanol treatment of mice lasted for about nine (9) days before mortality occurred while, that of alkaloid and flavonoid lasted for about five (5) days respectively subsequent to mortality. Consequently, the in vivo anti-trypanosome activity of methanol, alkaloid and flavonoid extracts did not eradicate the parasite in the blood of the poisoned mice but, appear to have prolonged the life of the treated animal when compared with the infected untreated group. Therefore, methanol extract of Sarocephalus latifolius leaf having the most influence on mice has illustrated more potential in anti-trypanosome activity which can be utilize in controlling African trypanosomiasis.