The study was aimed at evaluating the toxicological and antioxidant activities of Antiaris africana Engl. (family Moraceae), that is used in Nigeria and other West Africa countries as a panacea for the treatment of several ailments. The methanolic extract of A. africana (MEA) obtained was analysed for antioxidant activities in vitro and screened for various phytochemicals present. Phenolic and flavonoid contents were determined followed with high performance liquid chromatography -diode-array detection (HPLC-DAD) fingerprinting of phenolic content. Furthermore, the sub-acute toxicity of MEA was determined via oral administration of varying doses for 14 consecutive days (0, 50, 100, 200 and 400 mg/kg) in rats. After oral administration for 14 consecutive days in male rats, the toxicity effect was assayed by determining aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for hepatic function; urea and creatinine for renal function; creatinine kinase (CK) for cardiac function; and lipid profile. HPLC results showed that the major phenolics present are quercetin, rutin, caffeic acid, garlic acid and quercetin. MEA was able to scavenge diphenyl picryl hydrazyl, hydroxyl and nitric oxide radicals and prevent lipid peroxidation induced by ferrous sulphate at all concentration tested. The toxicology investigation showed that at low doses, A. africana is non-toxic, while at high doses; it is moderately toxic to the animals. In conclusion, A. Africana is generally non-toxic; however, care must be taken in administration at higher doses.Keywords: Toxicology, HPLC, phytochemicals, Antiaris african