Background: Oral mucositis (OM) is a common complication in cancer patients receiving radiotherapy or chemotherapy, impacting treatment outcome. Prevention and treatment of OM is an urgent problem in the field of anticancer therapy. This study aimed to evaluate the efficacy of honey with or without propolis in prevention and treatment of OM. Patients and methods: This study was conducted at the Oncology Center, Mansoura University.  Eighty patients were included and were classified into three groups: First group consisted of 30 patients, received pure natural commercial honey (40 ml divided into 4 times daily); Second group (30 patients), received same amount of honey in addition to propolis (0.5gram) and the third group (control group; 20 patients), only kept oral hygiene, or received anesthetic agents including benzocaine or lidocaine gel. Treatment started on the first day of chemotherapy or radiotherapy and continued for 3 weeks. Results: Among the whole group of patients, forty-two patients developed OM. There was significant difference in the occurrence of mucositis among groups in favor of patients in both experimental groups (50%, 36.6 % and 80% in groups 1, 2 and 3; respectively). Severe mucositis was lower among patients in the study group (23.1%) compared to the control group (31.3%). Conclusion: Oral intake of honey is valuable in reducing incidence and severity of oral mucositis compared to oral hygiene. Enrichment with propolis further decreases OM.