<p>Neuropathic pain has a complex pathogenesis and poses significant treatment challenges. In recent years, exercise has garnered increasing attention as a nonpharmacological intervention for the management of neuropathic pain. This review systematically examines the research progress on the neurobiological mechanisms of exercise in the treatment of neuropathic pain, including its effects on improving neuroinflammation, alleviating oxidative stress, modulating neuroplasticity, influencing the descending pain modulation system, and regulating gene expression and epigenetic modifications. Additionally, this review summarizes the application and therapeutic effects of various exercise interventions in different types of neuropathic pain, such as neuropathic pain after spinal cord injury, chemotherapy-induced peripheral neuropathy, diabetic peripheral neuropathy, and neuropathic pain in multiple sclerosis, on the basis of current clinical research. It also explores future research directions and trends in this field. By integrating basic research and clinical evidence, this review aims to provide a theoretical basis and practical guidance for exercise therapy in patients with neuropathic pain. Although existing evidence supports the analgesic potential of exercise, future high-quality clinical studies are needed to optimize individualized exercise prescriptions and further explore its molecular and neural circuit mechanisms.</p> Graphical Abstract <p>Mechanism and clinical application of exercise therapy for neuropathic pain. Exercise exerts analgesic effects through multiple mechanisms, including modulation of neuroinflammation, oxidative stress, neuroplasticity, descending pain modulatory system, and epigenetics. For neuropathic pain of different etiologies, exercise programs can be customized to accurately regulate specific pathological links.</p> <p></p>