Aim: The aim of this study was to assess the antioxidant effects of aqueous, ethanolic and methanolic extracts of Morus mesozygia Linn. Stapf. Twigs in Streptozotocin-Induced Diabetic Rats. Study Design: The study is an experimental case-controlled study. Place and Duration of Study: This study was carried out at the Biochemistry Research Laboratory, University of Port Harcourt, Rivers State, Nigeria, between June, 2018 and April, 2019. Methodology: A total of 65 male albino rats that weighed between 150g to 200g were used for this research study. Three different extracted solvents; aqueous, ethanolic and methanolic twig extracts were administered to different groups of the rats. The male albino rats for this study were induced with a single dose of 40mg/kg b.wt, intraperitoneally of streptozotocin in 0.1M of citrate buffer, pH 4.5. The diabetic male rats were those whose fasting blood glucose (FBG) were from 250mg/dl or 13mmol/L and above. They were then divided into different groups and treated with different concentrations of aqueous, ethanolic and methanolic extracts of the plant material. At the end of treatment period, the rats were kept on fasting for 6 hours prior to the process of euthanasia, they were sacrificed and blood samples were collected through cardiac puncture for analysis into lithium heparin bottle for the estimation of oxidative stress markers, malondaldehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), and antioxidant enzymes, superoxide dismutase (SOD), total antioxidant capacity (TAS). Statistical analysis was done using GraphPad prism (version 6.1) software. Data generated were represented as mean and standard deviations (Mean ±S. D). Level of significant at Tukey’s Multiple Comparative Test was tested at p<0.0001. Charts were made possible with the application of Minitab version 2019. Results: The results showed that there were significant increases in the levels of superoxide dismutase (SOD, 414.2±1.30) ng/ml, total antioxidant status (TAS, 82.97±7.71) mU/ml, total oxidant status (TOS, 355.02± 14.02) mU/ml activity, a reduced oxidative stress index of 4.29±0.26 and concentration of malondialdehyde (MDA of 18.67± 0.26mmol/L) when rats were treated with 400mg/kg of aqueous leaves of Morus mesozygia Linn. S. When compared with those of rats treated with 200mg/kg of aqueous leaf extracts of MMLS. there was a significant increases and decreases respectively. Other methods of extractions (methanolic and ethanolic), also improved the antioxidant statuses of the diabetes induced and treated rats after treatment of the extracts. Conclusion: The three extracts of Morus mesozygia Linn. S showed tremendous antioxidant effects against Streptozotocin-induced diabetic rats, with the methanolic extract showing the most potent effect.