Genetic mutations are linked to cancer. We evaluated gum arabic (GA) and eugenol (EUG) on systemic genotoxicity (spleen, kidney, lung) in rats with DMH-induced colorectal carcinogenesis. The prevention arm, once a week for 20 weeks, the controls received saline while the experimental groups received DMH at 20 mg/kg. During the same period and for an additional 9 weeks, the animals received water, GA, EUG or GA + EUG. The treatment arm, once a week for 20 weeks, the controls received saline while the experimental groups received DMH at 20 mg/kg. During the subsequent 9 weeks, the animals received water, GA, EUG or GA + EUG. The spleen, kidneys and lungs were harvested for genotoxicity evaluation. Genotoxicity was significantly less severe in spleen and kidney tissue in Group VIII and in Group XII, reflecting the synergistic antioxidant and antigenotoxic effect of GA and EUG administered in rats with DMH-induced colorectal carcinogenesis.