Vitamin D is increasingly recognized as a crucial factor in immune regulation, particularly in the context of autoimmune diseases. In addition to its well-established role in bone metabolism and calcium homeostasis, recent research highlights its significant influence on both adaptive and innate immune responses. In conditions such as multiple sclerosis, type 1 diabetes, and systemic lupus erythematosus, vitamin D enhances the function of regulatory T cells and suppresses pro-inflammatory cytokines, contributing to immune balance. Genetic factors also play a vital role in susceptibility to autoimmune diseases. Studies have investigated the interaction between vitamin D signaling pathways and genetic variants in immune-related genes, including the vitamin D receptor (VDR), vitamin D binding protein (VDBP), 25-hydroxylase (CYP2R1), and 1α-hydroxylase (CYP27B1) genes. Polymorphisms in these genes can alter vitamin D signaling, potentially affecting disease susceptibility and severity. This chapter explains the complex relationships among serum vitamin D levels, genetic variations, and immune regulation in autoimmune disorders. These findings emphasize the importance of further research to clarify the underlying molecular mechanisms and develop tailored therapeutic strategies. A deeper understanding of these interactions could pave the way for innovative preventive and therapeutic approaches for individuals with a genetic predisposition to autoimmune conditions.