This work investigated the therapeutic effects of flavonoid-rich extracts obtained from Hibiscus sabdariffa L. leaves in streptozotocin-induced diabetic rats. Their biochemical parameters such as redox stress biomarkers, anti-inflammatory levels, pancreatic histology, insulin concentration, lipase activity, purinergic enzyme activities, homeostasis model assessment of β-cells (HOMA-β), and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed. Furthermore, the relative gene expressions of insulin receptors and GLP-1 were examined. H. sabdariffa extracts significantly (p<0.05) mitigated redox stress and inflammation in diabetic rats, as indicated by the reduction in malondialdehyde (MDA) levels, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) as well as enhancement of reduced glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), and glutathione peroxidase (GPx). Pancreatic histological analysis revealed that the extracts protect against the degeneration of pancreatic acinar cells and beta cells. Moreover, they enhance pancreatic insulin concentration and reduce lipase activity in diabetic rats. In addition, the extracts positively affected purinergic enzyme activities, specifically ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ATPase besides significantly improving the homeostasis model assessments of β-cells and insulin resistance. Most notably, diabetic rats treated with H. sabdariffa leaf extracts activated the relative gene expressions of insulin and GLP-1 receptors. Hence, these findings support the potential of H. sabdariffa leaf extracts as a natural therapeutic agent for managing diabetes.