Background: Aloe vera has been widely used to treat various conditions such as sunburn or radiation-related dermatitis, mucositis, or esophagitis. It is suggested that Aloe vera may be benefit for radiation-induced mucositis. Objective: To evaluate the efficacy of oral aloe vera juice in the alleviation of radiation induced mucositis in head and neck cancer patients using a double-blind, randomized controlled trial. Methods and materials: Sixty-one eligible head and neck cancer patients, who received conventional radiation therapy at Ramathibodi Hospital, were randomized to receive oral Aloe vera juice or placebo. Mucosal reaction was assessed during the course of radiation using the Radiation Therapy Oncology Group grading system. Results: Patient baseline characteristics were identical in Aloe vera juice and placebo groups except in the gender. The incidence of severe mucositis was significantly lower in the aloe vera group compared with the placebo group (53% vs. 87%, p =0.004). However, there was no significant difference in the time-duration to severe mucositis development. No adverse effects related to the drug were observed. Conclusion: Oral aloe vera juice was beneficial in alleviating the severity of radiation-induced mucositis and without side effects. The Aloe vera juice may be an alternative agent treating radiation-induced mucositis in patients with head and neck cancers.