INTRODUCTION: A significant increase of 61.6 % in new cases of head and neck cancer (HNC) worldwide is projected by 2050. Multimodal treatments for HNC often result in debilitating oral side effects like oral mucositis (OM). Photobiomodulation (PBM) therapy shows promise in managing these side effects, yet standardized protocols are lacking. This randomized clinical trial aims to evaluate PBM's effectiveness in preventing and treating oral side effects and related symptoms in HNC patients. METHODS: We compared PBM with standard treatment in HNC patients at a single centre. PBM efficacy was evaluated on OM, pain, dysgeusia, hyposalivation, dry mouth, and trismus. Additionally, we controlled for analgesic use and fungal infection presence. The study adhered to the CONSORT checklist, is registered on the ClinicalTrials platform, and statistical analysis was performed using SPSS. RESULTS: The study included 53 patients. The PBM group experienced a significant reduction in OM progression, better salivary function preservation, and lower severity of pain and dysgeusia by the end of treatment. However, no significant differences were found between the PBM and standard treatment groups regarding xerostomia, trismus, analgesic use, or oral candidiasis incidence. CONCLUSION: PBM showed effectiveness in delaying onset and reducing the severity of oral mucositis and hyposalivation, as well as alleviating pain and dysgeusia at critical moments. However, it had no significant impact on xerostomia, trismus, analgesic use, or oral candidiasis.