The stem barks of Securidaca longepedunculata are used traditionally across Africa for the treatment of diabetes, cancer, metabolic diseases and asthma. This study was aimed at investigating the potential enzyme activities of the S. longepedunculata on the small intestine. Aqueous extracts of S. longepedunculata were tested in vivo on animal models: A total of 12 Wister rats were assigned into four (I–IV) groups of three animals each. Group I served as the control and was administered 0.5mL of distilled water. Groups II–IV were given 0.5, 1 and 2mg/kg body weight of S. longepedunculata stem bark extracts. The activities of the following enzymes, Alanine transaminase (ALT), Lactate dehydrogenase (LDH), Alkaline phosphatase (ALP), Aspartate transaminase (AST), were assayed in the small intestine. The result revealed a significant reduction in ALP and LDH. This gives an indication that the administration of aqueous extract of securidaca longepedunculata can elicit detrimental effect in the small intestine of the albino rat. Also the result obtained in the qualitative analysis shows the presence of phytochemicals such as: saponin, flavonoid and terpernoid.