Abstract Background The use of Loranthus micranthus in folklore medicine for treatment of diabetes and its associated complications is a common practice around the world. The present study investigated this traditional affirmation by in vivo investigation into the effect of L. micranthus leaf extract on hepatic and renal, oxidative status and glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes mellitus was induced in adult male Wistar rats by intraperitoneal injection of STZ (60 mg/kg). The diabetic rats were thereafter treated orally once per day with 5 mg/kg gilbenclamide or L. micranthus leaf extract (100 or 200 mg/kg) and monitored for 14 days. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress parameters, glucose metabolism enzymes and histopathologic examination of the liver and kidney were evaluated to monitor treatment-related effects of L. micranthus leaf extract in STZ-induced diabetic rats. Results Loranthus micranthus leaf extract administration significantly ameliorated hyperglycemia-mediated damage by decreasing the blood glucose level (45.9% and 84.7% on days 7 and 14 posttreatment, respectively), enhancing the antioxidant status, inhibiting lipid peroxidation and improving the architecture of the liver and kidney in STZ-induced diabetic rats. Furthermore, intervention of L. micranthus leaf extract restored the liver and kidney function biomarkers and increased the plasma levels of triiodothyronine and thyroxine to normal control in STZ-induced diabetic rats. Conclusions The findings from this investigation provide credible scientific support for the traditional use of L. micranthus leaf extract in the treatment of diabetes and its associated complications.