<p>Vitamin D and calcium play essential roles in glucose metabolism and insulin secretion, though the epidemiological evidence remains inconclusive and their direct molecular interaction with the insulin receptor remains unclear. This study aimed to investigate the effects of vitamin D and calcium supplementation on glycemic control and insulin sensitivity in Iraqi patients with type 2 diabetes mellitus (T2DM) and explore the potential binding affinity of vitamin D3 to the insulin receptor through molecular docking analysis. A total of 300 vitamin D-deficient T2DM patients were assigned to three groups based on the treatment protocol: Group A (metformin only), Group B (metformin + vitamin D), and Group C (metformin + vitamin D and calcium). Glycemic parameters, including fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FI), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), were evaluated before and after eight months of supplementation. Results showed that vitamin D supplementation significantly improved insulin secretion and sensitivity showing decreased FBG and HbA_1c with increased FI in group B patients, with Group C demonstrating the most pronounced improvements in FBG, HbA_1c, FI, and HOMA-IR. Molecular docking analysis revealed a strong binding affinity (-7.5228381 Kcal/Mol) of vitamin D3 to the insulin receptor, suggesting a potential direct role in insulin signaling. In conclusion, these findings highlight the combined benefits of vitamin D and calcium in improving glycemic control and insulin function in T2DM patients while providing novel molecular insights into vitamin D3’s interaction with the insulin receptor.</p>