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Alstonia boonei De Wild is a herbal medicinal plant grown abundantly in tropical countries and it is used by traditional medical practitioners in the treatment of many diseases. This study is aimed at investigating the Thin Layer Chromatography (TLC) profile, in vivo antioxidant and antidepressant activities of A. boonei stem bark extract. All experiments in this study were carried out using standard methods. The stem bark extract of A. boonei was successfully prepared by maceration using ethyl acetate as the solvent with % yield of 2.32. In the study of the Thin Layer Chromatography (TLC) profile, this was developed using the mixture of ethyl acetate and hexane in different ratios. The result showed three spots on the TLC plate which indicated the presence of at three compounds at 0.2, 0.33 and 0.38 Rf values. In the in vivo antioxidant study, the results showed a significant increase in the Superperoxide dismutase, Catalase, and Glutathione peroxidase level in the groups treated with ethyl acetate extract at (25, 50 and 100 mg/kg). However, the level of Malondialdehyde decreased with increase dosage of the leaf extract, indicating 100 mg/kg as the concentration with the highest anti-oxidant potential. In the antidepressant study,the Force Swim Test and Tail suspension Test of the ethyl acetate stem bark extract of A. boonei at (25, 50 and 100 mg/kg) showed a significant reduction in immobility time. The 100 mg/kg dose showed the lowest immobility time in the mice, indicating 100 mg/kg as the concentration with the highest antidepressant potential. The result obtained confirms the ethno medicinal use of the stem bark extract of A. boonei for the management of antioxidant related diseases and depression.