This work describes a study carried out to determine the antioxidant properties, xanthine oxidase and pancreatic lipase inhibitory potential of crude ethanol extract of Manihot esculenta matured leaf, in vitro. Antioxidant potential of the extract was ascertained using the 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and the nitroblue tetrazolium (NBT) assays. Xanthine oxidase (XO) inhibitory potential of the ethanol extract was assayed spectrophotometrically using a continuous time scan mode at 293 nm under aerobic condition; while porcine lipase was employed for the determination of its lipase inhibitory activity. The extract showed moderate antioxidant activity against DPPH (40.42±0.43%) and promising superoxide scavenging activity against NBT (94.76±0.44%) compared to different standard antioxidants including butylated hydroxylanisole (BHA), uric acid (UA), curcumin (CUR) and ascorbic acid (ASC). This extract showed mild (50.70±0.48%) xanthine oxidase inhibitory activity in comparison to allopurinol (92.1±0.35%), standard inhibitor of XO. Inhibition of porcine pancreatic lipase by Manihot esculenta leaf extract was significantly lower than that of the standard drug, Orlistat (67.53±0.22% and 94.81±0.78%, respectively). The results demonstrated that Manihot esculenta leaf extract is a promising source of antioxidants, xanthine oxidase and pancreatic lipase inhibitory agents.