Metabolic syndrome, primarily driven by high-fat/high-sugar (HF/HS) diets, is closely linked to insulin resistance and renal injury, leading to serious complications such as type 2 diabetes mellitus and diabetic nephropathy. This study explored the combined effects of Vitamin D (VD) and dapagliflozin (Dap) on metabolic and renal complications in an HF/HS diet-induced rat model of metabolic syndrome. The combination therapy significantly improved insulin sensitivity, reduced fasting blood glucose levels, and alleviated renal injury markers such as blood urea nitrogen and creatinine. It also attenuated inflammation, lipid accumulation, and endoplasmic reticulum stress in renal tissues, as evidenced by reduced levels of inflammatory cytokines and key stress markers (GRP78 and CHOP). Importantly, the study highlights the novel synergistic potential of VD and Dap in addressing these complications through complementary mechanisms. These findings suggest that this combination therapy offers promising clinical potential for managing metabolic syndrome and its progression to severe complications.