Background <p>Chemotherapy-induced peripheral neuropathy (CIPN) particularly from platinum-based agents remains a major dose-limiting complication, impairing patients’ quality of life. This double-blind randomized clinical trial evaluated the neuroprotective potential of curcumin, a natural polyphenol with antioxidant and anti-inflammatory properties, in mitigating platinum-induced peripheral neuropathy in cancer patients.</p> Methods <p>Seventy adult cancer patients with established platinum-induced CIPN were randomly assigned to receive either curcumin (40&#xa0;mg twice daily) or placebo for four weeks in a double-blind design. Neuropathy symptoms were assessed using the validated QLQ-CIPN20 questionnaire at baseline and during follow-up (days 4, 7, 14, and 28).</p> Results <p>Of 70 randomized patients, 65 completed the study (31 in the curcumin group and 34 in the placebo group). By day 28, the curcumin group demonstrated a significant reduction in sensory symptom scores compared with placebo (<i>p</i> = 0.021), along with a decrease in total QLQ-CIPN20 scores (<i>p</i> = 0.0012). No significant changes were observed in motor or autonomic domains.</p> Conclusion <p>Curcumin significantly alleviated sensory symptoms of CIPN, suggesting a potential neuroprotective effect. Although only patient-reported outcomes were evaluated, the results provide preliminary clinical evidence supporting curcumin as a safe adjunctive option for managing CIPN. Future studies incorporating objective neurophysiological or biomarker assessments are warranted to validate these findings.</p> <p><i>Trial Registration</i>: Trial Registry Number (IRCT20191106045356N6||<a href="https://irct.behdasht.gov.ir/">https://irct.behdasht.gov.ir/</a>) with the Clinical Trial Registry 2022-08-29.</p>