This work was aimed at determining the antioxidant activity of an ethanol extract of Tetrapleura tetraptera fruits in rats administered DMH. Group 1 (positive control) contains rats without the administration of DMH, extract, or CMC. Group 2 (negative control) received DMH, 1 ml of 1% CMC, and no extract. Group 3 received a low dose of the ethanol extract of Tetrapleura tetraptera fruits (100mg/kg) and DMH. Group 4 received a high dose of the ethanol extract of Tetrapleura tetraptera (200mg/kg) and DMH. The DMH was administered once a week for four consecutive weeks, while the ethanol extract of Tetrapleura tetraptera was administered daily for four consecutive weeks. The result showed that there was a significant increase in the activities of SOD, CAT, and GST in rats administered an extract of Tetrapleura tetraptera fruits compared to the negative control group. In general, the introduction of Tetrapleura tetraptera to the rats caused an increase in the activity of the antioxidants compared to the negative control. The histopathological profile, however, showed that the DMH did not affect the liver, colon, and small intestine morphology. It could thus be concluded that the ethanol extract of Tetrapleura tetraptera fruit has potent antioxidant activity.