Introduction: Mucositis is acute oral toxicity induced by radiation or systemic cytotoxic chemotherapy agents in patients with cancer that may lead to discontinuing the treatment or reducing the administered dose. In this study, we aimed to evaluate the preventive effect of oral L-carnitine on chemotherapy-induced mucositis. Methods: This prospective clinical trial employed a double-blind, randomized, placebocontrolled design. All consecutive cancer patients who met the inclusion criteria were enrolled in the oncology ward of Imam Khomeini Hospital, Urmia, Iran. Patients were randomly allocated to one of two groups: one receiving L-Carnitine 1000 mg three times daily (total dose 3000 mg/day) and the other receiving a placebo. Mucositis severity was evaluated clinically using the WHO scoring system every week throughout the 21-day study period. Results: L-carnitine supplementation did not significantly reduce the incidence of mucositis compared to placebo (p-value = 0.748). Among the 40 enrolled patients, 20 (50%) developed mucositis: 9/16 (56.25%) in the L-carnitine group and 11/24 (45.83%) in the placebo group. Grade 2 mucositis was the most common presentation, affecting 31.3% (5/16) of the L-carnitine group and 29.2% (7/24) of the placebo group. Conclusion: Our investigation did not identify a statistically significant impact of L-Carnitine supplementation on the incidence, severity progression, or WHO grade distribution of chemotherapy-induced oral mucositis compared to the placebo group.