Oxidative stress plays an important role in both induction of diabetes and development of diabetes complications. This study evaluated the effect of leaf extract and fractions of M. cecropioides on both chemical and disease induced oxidative stress. The leaves were extracted with methanol and partitioned into various fractions. Phytochemical analysis and total phenolic content (TPC) were done for the extract and fractions. The DPPH (2,2-diphenyl-1-picrylhydrazyl) and Ferric reducing antioxidant power assay were used to evaluate their in vitro antioxidant potentials of the extracts and fractions at 52.5, 125, 250, 500 and 1000 µg/ml concentrations with ascorbic acid as reference standard. Carbon tetrachloride and streptozotocin-Nicotinamide (STZ-NAD) were used to induce chemical and diabetes induced oxidative stress respectively. Treatments were done with 200 and 400 mg/kg of the extract and fractions using Silymarin as reference standard. Liver function tests and lipid peroxidation (LPO) were used to monitor CCL4 induced oxidative stress while serum antioxidant enzymes (catalase and superoxide dismutase), LPO and total plasma antioxidant assays were used to monitor diabetes induced oxidative stress. The ethyl acetate fraction (EAF) showed the highest TPC of 386.06 mgGAE/g. The EAF and butanol fraction (BF) showed better DPPH activity compared to the extract with IC50s of 49.78, 71.57, 98.92 µg/ml respectively. The EAF both at 200 and 400 mg/kg maintained non-significant (p > 0.05) difference between pre-induction and post-induction ALT and AST concentrations. Also, only EAF at 400 mg/kg protected against significant rise in CCL4 induced LPO from baseline values which was not achieved with 100 mg/kg silymarin (reference standard treatment). The EAF at 400 mg/kg was the only treatment that produced significant (P<0.05) reduction in blood glucose 24 h post-treatment compared to vehicle control group. The EAF and BF at 400 mg/kg just like 200 mg/kg metformin were able to restore serum catalase almost to their pre-induction values with no significant (P>0.05) difference. M. cecropioides proved effective in both chemical and disease induced oxidative stress.