Objective: In diabetes, oxidative stress played a key role in their pathogenesis. Naringin, a major flavanone glycoside in citrus species, several literatures revealed their strong antioxidant potential in animal models of oxidative stress. The aim of the present study was to develop, characterize and evaluate the beneficial effects of naringin loaded solid lipid nanoparticles (N-SLNs) in insulin deficient Diabetic mice. Methods: The using of Streptozotocin (STZ) in mice causes β-cell apoptosis, oxidative stress and inflammatory response. Administration of N-SLNs counteracted STZ-induced β-cell apoptosis via inhibiting the mitochondrial and death receptor mediated pathways. Results: N-SLNs founds of 250 nm of average particle size and 87% encapsulation efficiency with controlled drug release. Moreover, N-SLNs observed 6 times higher levels of naringin in blood compared to when administered as free naringin. In addition of these, they showed beneficial effect with the suppression of DNA damage response, nuclear factor-kappa B, and mitogen-activated protein kinase-mediated signalling pathways as well as significant reduction of reactive oxygen species accumulation in the pancreas. Conclusion: Therefore, the results demonstrated that N-SLNs could be a nanotool and promising therapeutic strategy to protect pancreatic β-cells against oxidative stress-induced apoptosis in diabetes.