The purpose of this study was to investigate the effects of royal jelly against radiation-induced oral mucositis in rats. This study was comprised of 48 adult male Sprague-Dawley rats, each between eight and 12 weeks old and weighing 275±35 g. These were divided randomly into six groups; Group C (control), Group IR (irradiation), Group IR+RJ50 (irradiation plus 50 mg/kg royal jelly), Group IR+RJ100 (irradiation plus 100 mg/kg royal jelly), Group RJ50 (50 mg/kg royal jelly), and Group RJ100 (100 mg/kg royal jelly). The degree of mucositis, the animal's body mass, and food intake were evaluated. Biochemical and histopathological methods were utilized for the evaluation of mucositis, and a hemogram, oxidative stress markers, and biochemical parameters were analyzed. Tongue samples were also processed for histopathological examination. Irradiation significantly increased oral mucositis, decreased the thrombocyte and neutrophil counts, and resulted in a reduction of food intake accompanied by weight loss. In addition, a significant increase in malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) and catalase (CAT) activities were found (p< 0.001). Irradiation plus 50 mg/kg royal jelly caused normalization in the quantitative, biochemical, and histopathological parameters compared with the group that underwent irradiation alone.Irradiation plus 100 mg/kg royal jelly did not provide superior radioprotection against radiation-induced toxicities. Royal jelly was administered orally to reduce oral mucositis as it may be more suitably applied. International Journal of Hematology and Oncology INTRODUCTION Radiotherapy (RT) is an essential therapeutic modality in the management of head and neck cancers. Despite advances in RT technology, oral mucositis has not been ameliorated in head and neck cancer patients treated with radiotherapy. The current head and neck radiotherapy protocols have a mucositis incidence of 85-100%. The severity of mucositis depends on many variables, such as anti-cancer treatment protocol, age, diagnosis of the patient, level of oral hygiene during therapy, and genetic factors.