The current study investigates the effects of ethanolic extract of M. concanensis Nimmo leaves (EEMCNL) with respect to its potent protective tissue damage, antioxidant properties in serum, liver and kidney, histopathological evaluation, and PPARγ and GLUT4 gene expression in liver and pancreatic tissue of Streptozotocin-Nicotinamide (STZ-NA) induced diabetic rats. Animals were divided into five groups (n = 5): control; diabetic; diabetic + EEMCNL; control + EEMCNL; and diabetic + glibenclamide. After 45 days of treatment with EEMCNL, MDA levels were significantly decreased in the diabetic-induced group when compared with the STZ-induced diabetic group ( P   <  0.05). The activities of serum enzymes AST, ALT, ALP, ACP and LDH were significantly decreased in serum and kidney, and increased in liver tissues of the EEMCNL-treated group as compared with the STZ-NA induced diabetic group ( P   <  0.05). The levels of total protein, urea, creatinine and uric acid observed in the diabetic group returned to normal by administration of EEMCNL (250 mg/kg) as relative to the STZ-NA induced diabetic group ( P   <  0.05). Furthermore, EEMCNL upregulated PPARγ and GLUT4 expression in liver and pancreatic tissue of the STZ-NA induced diabetic group rats. Taken together, these findings contribute to a better understanding of the hepatoprotective and renoprotective potential of EEMCNL against oxidative stress in the diabetic state, which was evidenced by the capacity of EEMCNL to modulate the antioxidant defence and to decrease lipid peroxidation in these tissues.