Background: Human exposure to arsenicals, its toxicity, subsequent adverse effects on health has been widely reported and implicated in the etiology of several cancers. Objectives: We investigated the effect of Aframomum longiscapum (AL) extracts on sodium arsenite (SA) and ethanol (EtOH)- induced toxicities in rats. Materials and Methods: Male rats were fed SA, EtOH, and SA + EtOH, with or without AL for 5 weeks. Hepatic transaminases were assessed in serum, micronucleated polychromatic erythrocytes (mPCEs) from bone marrow, liver histopathology, and semen quality from caudal epididymis were assessed, respectively, and data were represented as mean ± SD, analyzed by ANOVA. Results: SA, SA + EtOH, and AL alone induced mPCEs formation in rat bone marrow (P < 0.05). A decrease (P < 0.05) in mPCEs in AL + SA + EtOH-treated rats compared with SA, and SA + EtOH was observed. SA and EtOH treatment increased serum hepatic transaminases (P < 0.05) relative to control, while AL treatment resulted in a decrease (P < 0.05). AL, SA, and SA + EtOH treatment decreased sperm count and motility (P < 0.05) with no effect on viability compared with control. Semen morphological abnormalities showed no difference (P > 0.05) across the treated groups. Hepatic histopathology indicated mild mononuclear cellular infiltration in the control group. Necrotic hepatocyte were observed in SA, SA + EtOH treated groups, with no visible lesions seen in the AL treated group. Mild hepatocyte congestion of the portal vessels was observed in AL + SA + EtOH-treated groups. Conclusion: The AL extract exhibited anticlastogenic and hepatoprotective potentials, reduced sperm count, motility, with no effect on viability and morphology. Our findings suggest that AL may mitigate the effect of arsenicals-induced clastogenicity implicated in chemical carcinogenesis.