Diabetic neuropathy, a common complication of diabetes mellitus (DM), involves nerve damage resulting from prolonged exposure to high blood sugar levels. Genetic factors play a crucial role in influencing susceptibility to this condition. Variations in genes related to nerve structure and function, inflammatory responses, and metabolic processes have been implicated in diabetic neuropathy. For instance, polymorphisms in the gene encoding protein kinase C beta (PKC-β) contribute to increased vulnerability by promoting oxidative stress and inflammation in nerve tissues. Similarly, genetic variations in the aldose reductase gene (AKR1B1), involved in the polyol pathway, may disrupt glucose metabolism and contribute to nerve damage. Furthermore, genes regulating neurotrophic factors like nerve growth factor (NGF) and those affecting mitochondrial function and oxidative stress responses also influence neuropathy risk. Understanding these genetic underpinnings not only enhances our knowledge of diabetic neuropathy’s pathophysiology but also opens avenues for personalized therapeutic strategies aimed at mitigating its impact. Continued research into the interplay of genetic predisposition and environmental factors promises further insights into preventing and managing this debilitating complication effectively.