Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, debilitating toxicity of neurotoxic chemotherapy that causes persistent pain and sensory loss. Pharmacologic options (e.g., duloxetine) provide only modest relief, underscoring the need for new therapies. We investigated three integrative interventions—acupuncture, paeonol, and topical menthol— examining mechanisms and clinical efficacy for CIPN. Methods: We performed preclinical and clinical studies. Clinical efficacy of acupuncture was evaluated in a randomized, sham controlled trial in taxane-treated breast cancer patients (n=20) receiving 15 sessions over 9 weeks. Outcomes included Semmes Weinstein monofilament (SWM) thresholds and the Brief Pain Inventory–Short Form (BPI-SF). Mechanistic studies tested electroacupuncture (EA) and paeonol in paclitaxel-induced CIPN mouse models. A pilot study assessed a topical menthol glove for tactile sensation. Results: Acupuncture: Compared with sham, manual acupuncture significantly reduced pain severity (BPI-SF) and improved SWM tactile thresholds in hands and feet. In mice, 10 days of EA (two 5-day courses separated by a 2-day washout) attenuated paclitaxel-induced mechanical allodynia and suppressed spinal cord TNF-α and the apoptosis marker Bax. Paeonol: Oral paeonol reversed mechanical and thermal allodynia in paclitaxel-treated mice; its effect was absent in adiponectin-knockout mice. Paeonol increased circulating adiponectin and upregulated p-AMPK in spinal cord and dorsal root ganglia, indicating activation of the adiponectin/AMPK pathway. Topical menthol: In a pilot study, menthol glove use improved tactile sensation, with benefits persisting up to one week after treatment. Conclusion: Across complementary preclinical and clinical investigations, acupuncture, paeonol, and topical menthol showed promise for alleviating CIPN. These integrative approaches reveal translatable neuroimmune and metabolic mechanisms and warrant confirmation in larger, definitive randomized trials.