ABSTRACT Angiotensin I Converting Enzyme (ACE) is a glycoprotein with peptidyl dipeptide hydrolase activity which cleaves Angiotensin I to produce Angiotensin II. Angiotensin II is a powerful vasoconstrictor that as well regulates the synthesis of aldosterone that consequently interferes with blood pressure regulation. This study evaluates the effect of aqueous extract of Combretummicranthum leaves and its fractions on the in vitro activity of rabbit ACE and the possible antioxidant potentials fractions. C. micranthum leaves were extracted using aqueous as solvent. Consequently, the in vitro ACE inhibitory activity of the extract was conducted using cushman and cheng method and the aqueous extract was further subjected to chromatographic fractionation where the fractions obtained were assayed for in vitroinhibitory activity against rabbit ACE and their possible antioxidant potentials. Aqueous extract of C. micranthumleaves produced 59.43Â±4.00 % inhibitory activity comparable to captopril which produced 83.02Â±2.67% activity. The chromatographic fractions A, B, C and D were able to inhibit the in vitro activity of rabbit ACE with the inhibitory percentages of 8.21Â±41.19, 97.69Â±8.57, 78.32Â±7.14 and 98.32Â±2.66 % respectively. Phenolic compounds were found in the various fractions of the aqueous extract of C. micranthum with fraction B having the highest amount of these phenolics. The antioxidant potency of these fractions was evident in their free radical scavenging IC50, reducing power ability and total antioxidant capacity which all showed that fraction B may possibly exhibit the highest antioxidant potency as compared to fractions C and D. The bioactive phytochemical constituents from the GC-MS analysis of fraction B of the aqueous extract of C. micranthum where found to be Megastigmatrienone, 3,5-Dimethoxy-4-hydroxyphenylacetic acid and Estra-1,3,5(10)-trien-17Î²-ol. Hence, the results demonstrated that aqueous extract of C. micranthum has shown the tendency to inhibit the in vitro activity of ACE which could be attributed to its antioxidant activity demonstrated by the reduction power and the total antioxidant capacity of the various fractions.