Medicinal herbs and green manufacturing of silver nanoparticles (AgNPs) are effective treatments for diabetes. Origanum majorana (OM) leaf extract is known for its potential medicinal benefits, including anti-diabetic activities. The study's objective was to assess the efficiency of OML extract and nanoparticles in diabetic rats induced with Streptozotocin (STZ), as well as their histological effects on Liver organ tissue. Methods: 25 Diabetic Rats were separated into 5gps: Group I: (n = 5) untreated (Non-diabetic Control), Group II: (n = 5) injected with Streptozotocin (STZ) untreated diabetic group, Group III: (n = 5) diabetic rats treated with the glibenclamide drug, Group IV: (n = 5) diabetic rats administration of OM leaf extract, Group V: (n = 5) diabetic rats administration of OM leaf extract nanoparticles. Various parameters including blood glucose levels, insulin, lipid profile, Liver and Kidney function test, antioxidant (MAD & GSH), and histopathological changes in the Liver were evaluated. Results: Both Origanum majorana leaf extract and its nanoparticles dramatically lowered blood glucose levels when compared to the untreated diabetic group. Treatment with OM leaf extract nanoparticles showed superior effects in improving insulin sensitivity, lipid profile, and Liver and Kidney enzymes compared to the extract alone. Additionally, both formulations exhibited MDA properties, as evidenced by decreased levels and increasing GSH levels. Histopathological examination revealed that OM leaf extract and its nanoparticles mitigated STZ-induced damage in liver tissue, with a noticeable reduction in inflammatory infiltrates and cellular degeneration. Conclusion: OM leaf extract and its nanoparticles demonstrate promising Anti-diabetic characteristics in diabetic rats triggered by STZ, along with protective effects against histopathological alterations in the liver. The nanoparticle formulation exhibits enhanced efficacy, possibly attributed to improved bioavailabilityFurther study is needed to explain the underlying processes and investigate their potential therapeutic applicability in diabetes control, while also taking into account the histopathological consequences