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Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to impaired insulin secretion and/or action. Conventional therapies are often limited by side effects, highlighting the need for alternative treatments. Natural products have gained interest as promising therapeutic agents. Spondias tuberosa Arruda (umbu), traditionally used in Brazilian folk medicine, exhibits pharmacological potential against metabolic diseases. This study evaluated organoprotective and antioxidant effects of S. tuberosa extract (ExSt) in streptozotocin (STZ)-induced diabetic rats through clinical, biochemical, histopathological evaluations, as well as analysis of oxidative stress-related markers. Fifty-two Wistar rats were divided into five groups: CT (nondiabetic control), DM (diabetic), EX (nondiabetic + ExSt), DMEX (diabetic + ExSt), and DMIN (diabetic + insulin). Diabetes was induced by STZ (50 mg/kg, i.p.), and treatments with ExSt (500 mg/kg, orally) or NPH insulin (10 IU, s.c.) were administered for 30 days. Diabetic rats exhibited hyperglycemia, polyphagia, polydipsia, weight loss, and increased transaminases (AST, ALT), along with hepatic and pancreatic alterations. Treatment with ExSt moderately reduced AST and ALT levels, strongly preserved pancreatic morphology, and attenuated hepatic glycogen depletion by 50% despite the maintenance of hyperglycemia. Additionally, ExSt downregulated TGF-β1 and TGF-β2 expression and modulated oxidative stress-related enzymes, indicating antioxidant and antifibrotic mechanisms. These findings demonstrate that S. tuberosa extract mitigates hepatic and pancreatic injury in experimental diabetes through modulation of oxidative enzymes and TGF-β signaling, supporting its potential as a natural therapeutic alternative derived from Brazil's biodiversity.