The purpose of this study was to investigate the in-vivo and in-vitro potentials of ethyl acetate extract of P. americana leaf in alloxan-induced diabetic rats. Quantitative phytochemicals analyzed includes; flavonoids, saponins, tannins, alkaloids and phenolics. Measurement of antioxidant activity using 1,1-Diphenyl-2-picrylhydrazyl, total antioxidant capacity, hydroxyl radical, hydrogen peroxide, superoxide radical and ferric reducing activity of the extract was carried out. Hyperglycemia was induced by intraperitoneal injection of alloxan monohydrate to albino rats. In-vivo anti-oxidant potentials of the extract were evaluated by measuring liver homogenate activity of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and malondyaldehyde in alloxan-induced diabetic rats administered with the extract. A total of 30 Albino rats were used for this experiment and they were divided into six groups of 5 rats each. Group A; normal control, Group B; diabetic control, Groups C-E; experimental groups administered with different doses (100, 200 and 400 mg/kg body weight respectively); of the extract and Group F; glucophage (84 mg/kg body weight, standard drug) for 4 weeks. This study was conducted in the Department of Biochemistry, Bayero University, Kano, in August, 2018. Data was analyzed using one-way ANOVA with P=.05 value considered as significant. Results of the quantitative phytochemical investigation shows that the extract is rich in phenolics (184.1±0.6), flavonoids (115.8±2.1), alkaloids (41.5±1.8), with least concentration of tannis (21.2±0.8) and saponins (15.2±2.3). The extract exhibited high radical scavenging activity against synthetic free radicals (DPPH), reactive oxygen species (peroxide, superoxide and hydroxyl acid) and high ability to reduce Fe3+ to Fe2+ (FRAP). The activities of antioxidant enzymes of the treated rats were increased significantly (P=.05) while the level malondyaldehyde was significantly decreased (P=.05) in the treated groups. Ethyl acetate leaf extract of Persea americana contains phytochemical substances which improved antioxidant status and can be use as herbal therapy for the management of oxidative stress induced by diabetes mellitus and associated complications.