Antioxidants have been found to terminate the attack of reactive oxygen species which have been implicated in the pathophysiology of many diseases. This study is reporting the antioxidant activity and the preliminary phytochemistry of the ethanol extract from the stem of Anchomanes difformis. The ethanol extract (ADES) was obtained by cold maceration and partitioned into: n-hexane (ADHS), dichloromethane (ADDS) and aqueous (ADAS) fractions. Free radical scavenging activity was done using the standard diphenylpicrylhydrazine (DPPH) spectrophotometric method with ascorbic acid as the standard for comparison. Phytochemical screening was done using standard phytochemical screening reagents. Chromatography (Column and thin layer) techniques was used for the separation of antioxidant compounds from the bioactive fractions with antioxidant activity identified after spraying the developed thin layer chromatography plates with DPPH. Infra-red (IR) spectroscopy was used for functional group characterization of the isolated antioxidant compounds. The significant {p<0.05) trend in free radical scavenging activity (IC50 mg/ml) was: ADHS (>10.0) ˂ ADES (> 10.0) ˂ ADAS (4.0) ˂ ADDS (1.8) ˂ ascorbic acid (<0.3125). Saponins, sugar derivatives and triterpenoids were present as class of phytochemicals with alkaloids, anthraquinones, cardiac glycosides and phenolics absent. From IR spectroscopy analysis, antioxidant component coded ADD1 isolated from the ADDS fraction was partially characterized to be an aromatic (but not phenolic) compound having either a hydroxylated aliphatic or glycosylated side chain while the antioxidant component ADA1 isolated from the ADAS fraction was partially characterized to be a glycoside derivative with a saturated ketone aglycone moiety. The ADES was relatively safe (LD50>5000 mg/kgbw). This result is suggestive that the ADDS and ADAS fractions are containing constituents that could act as good free radical scavengers and probably have the ability to inhibit the progression of tissue damage due to oxidative stress.