Green formulated silver nanoparticles offer a great promise in biomedicine. Administration of streptozotocin causes severe hepatotoxicity and nephrotoxicity by increasing the blood glucose. The development of nephroprotective drugs through eco-friendly production routes is a major challenge for current pharmacology and nanotechnology. The creation of cutting-edge technology for the synthesis of effective nephroprotective agents is crucial on a global scale. So in the current study, we report herein the bio-inspired proficient preparation of silver NPs over Pistacia atlantica (P.a.) aqueous extract as natural reducing/capping and stabilizing agent (P.a./Ag NPs) under ultrasonic irradiation. The final hybrid nanocomposite was thereafter characterized by a range advanced analytical methods like, FE-SEM, ICP-OES, EDX, TEM, and elemental mapping. Diabetes was induced by administration of 60 mg/kg of streptozotocin (STZ) intraperitoneally in 100 mature male mice and they were randomly divided into 5 groups. The negative control group received normal saline and treatment groups received glibenclamide with dose 0.5 mg/kg and 10 and 40 μg/kg of P.a./Ag nanocomposite through gavage for 50 days. On the last day, serum levels of samples blood glucose, urea and creatinine were measured. After tissue processing, 5 μm sections of the kidneys were prepared and they were stained by periodic acid Schiff (PAS) and used for stereological analysis. The kidney weight, kidney volume (Volume of cortex, medulla, glomerulus, proximal and distal tubules, collecting ducts, loop of Henle, interstitial tissues, and vessels) and kidney structures length (length of proximal and distal tubules, collecting ducts, loop of Henle, and vessels) decreased significantly (p ≤ 0.05) after treatment with high dose of P.a./Ag NPs nanocomposite (p > 0.05). The increased levels of blood glucose and urea were decreased (p ≤ 0.05) significantly in P.a./Ag nanocomposite-treated groups as compared to the untreated diabetic. This study suggested using from P.a./Ag nanocomposite as an antidiabetic and nephroprotective drug in the developing countries.