Background: The main objective of this study was to assess the impact of non-invasive photodynamic therapy by Curcumin and photo-bio-modulation low level (LL) laser treatment in managing oral mucositis induced by chemotherapy in pediatric patients. Methods: A cliinical trial was conducted involving 90 patients aged between 3 years and 15 years. The trial was open, controlled and blind. Patients were divided into two groups; Group A received photodynamic therapy, using Curcumin and a red laser at a wavelength of 450 nm, at 142 J/cm2, 100 mW. Group B received LL laser at a wavelength of 660 nm, delivering 1 joule of energy per point at 100 mW power output for 10 seconds. The results were assessed using both the World Health Organization (WHO) and Children’s International Mucositis Evaluation Scale (ChIMES). Statistical analysis included the Chi-square, Exact Fisher, Student’s t test and Mann-Whitney tests, as well as a mixed linear regression model for group comparisons, with a maximum allowable error of 5%. Results: There was no distinction observed between the groups in terms of the number of sessions required to achieve clinical resolution of oral lesions (p ≥ 0.05) or the reported reduction in patient pain (p ≥ 0.05). Nevertheless, within each group, a notable reduction in pain was evident (p ≥ 0.05). Conclusions: Photodynamic (PD)-and low level (LL) laser-therapy are viable options for managing oral mucositis (OM) in children and young patients. Both treatments were well-received and demonstrated positive outcomes in alleviating the pain associated with the condition. Clinical Trial Registration: A randomized clinical trial was register on ClinicalTrials.gov, ID NCT06044142. https://clinicaltrials.gov/study/NCT06044142.