Background <p>Oxidative stress is a key contributor to the progression of diabetes mellitus and its associated complications. Recently, S-adenosyl methionine (SAM) has shown promise in mitigating oxidative stress and improving glucose metabolism. This study aimed to investigate the effects of SAM supplementation on biochemical parameters, oxidative stress markers, and histopathological alterations in the kidneys and liver of streptozotocin (STZ)-induced diabetic rats.</p> Methods <p>Eighteen male Wistar rats were randomly divided into three groups (n = 6 per group): non-diabetic control, diabetic control, and diabetic rats treated with SAM (10 mg/kg/day, intraperitoneally) for 4 weeks. Fasting blood glucose, renal and hepatic biochemical markers (urea, creatinine, ALT, AST), and oxidative stress markers (malondialdehyde, protein carbonyls, total antioxidant capacity) were measured. Histopathological changes in kidney and liver tissues were also assessed.</p> Results <p>Diabetic rats treated with SAM exhibited minor, non-significant changes in fasting blood glucose, urea, creatinine, ALT, and AST levels. In contrast, treatment with SAM in diabetic rats significantly reduced malondialdehyde and protein carbonyl levels in both kidney and liver tissues compared to the diabetic control group (P &lt; 0.05). Furthermore, histopathological analysis revealed improved tissue architecture and reduced pathological changes in the diabetic group treated with SAM.</p> Conclusion <p>Our findings demonstrated that SAM supplementation exerts significant antioxidant and histopathological protective effects against diabetes-induced damage in kidney and liver tissues.</p>