This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa (kiwifruits) aqueous extract in streptozotocin-treated rats. Animals were distributed into; control, A. deliciosa aqueous extract (ADAE; 1 g/kg orally), streptozotocin (STZ; 50 mg/kg, i.p, single dose), and STZ plus ADAE, respectively. Results showed that ADAE had high antioxidant and radical scavenging potency. Elevation in blood sugar level, lipid peroxidation (LPO), kidney function biomarkers, and perturbations in hematological parameters were observed in diabetic rats. While, enzymatic and non-enzymatic antioxidants, protein content, and alkaline phosphatase (ALP) activity declined. Furthermore, histological, immunohistochemical alpha-smooth muscle actin immunoreactivity (α-SMA-ir) and histochemical (collagen, total protein, DNA, and RNA) alterations were observed in rat kidneys. Moreover, STZ produced upregulation of inflammatory associated genes (tumor necrosis factor-alpha; TNF-α and transforming growth factor β1; TGF-β1) and triggered apoptosis by upregulating apoptotic related gene [Bcl2-associated X protein (Bax)] and downregulating anti-apoptotic related gene B-cell lymphoma-2 (Bcl-2) based on real-time PCR data. Moreover, diabetic rats administered with ADAE showed significant restoration in LPO, antioxidant status, and biochemical indices besides tissue architecture, and genes improvement regarding STZ group. Conclusively, A. deliciosa has a valuable ameliorative influence and can restore glucose levels and improve kidney dysfunction in diabetic rats.