Objective To evidence the ability of ethanol fruit extract from Detarium microcarpum (D. microcarpum) to preserve DNA integrity against oxidative genomic damage. Methods Ethanol extract from D. microcarpum fruit pulp was analyzed for its antioxidant capacity using ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azinobis-3-ethyl-ethylbenzothiazoline-6-sulphonate, superoxide anion, deoxyribose degradation and lipid peroxidation models. The genoprotective activity was assessed ex vivo by comet assay, on liver cells of NMRI female mice using cyclophosphamide (CP) as genotoxic agent. Results Ethanol extract from D. microcarpum fruit pulp exhibited interesting antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl, deoxyribose degradation and lipid peroxidation assays. The extract did not present any genotoxic effect but protected DNA against CP-induced damages with a dose-dependent manner. The genoprotective effect observed was related to the antioxidant molecules of the fruit that scavenged the hydroxyl radical (generated by the metabolism of CP) as well as the peroxyl and alkoxyl radicals issued from lipid peroxidation. Other mechanisms such as inactivation of CP metabolism to genotoxic end products, induction of the expression of antioxidant and DNA repair enzymes have been discussed. Conclusions Our results suggest that the wild edible fruit from D. microcarpum could be beneficial on consumer's health by its antioxidant and genoprotective effects, particularly during chemotherapies exhibiting genotoxic effects like CP in cancer treatment.