Aims: To evaluate the effectiveness of xylitol nasal irrigation in alleviating sinonasal side effects and preserving quality of life in patients undergoing radiotherapy (RT) for nasopharyngeal cancer (NPC). Methodology: A double-blind, randomized controlled trial enrolled NPC patients receiving RT. Participants were randomized (1:1) to perform bilateral nasal irrigation twice daily with standard saline (control) or saline with 6 g of xylitol (intervention), from RT initiation to 4–6 weeks post-treatment. The primary outcome was the change in sino-nasal quality of life (SNOT-22 score). Secondary outcomes included patient satisfaction (VAS) and endoscopic scores for nasal discharge and edema. Data were collected at baseline, RT completion, and 4–6 weeks post-RT. Analysis utilized Generalized Estimating Equations (GEE) via intention-to-treat (ITT) and per-protocol principles. Results: Twenty-four participants were randomized (n=12/group) with well-balanced baseline characteristics and high compliance (>83%). In ITT analysis, sinonasal quality of life significantly deteriorated in the Saline group (mean SNOT-22 increase +10.75, p=0.037), but remained stable in the Xylitol group (+0.58, p=0.852). The between-group difference favored Xylitol (mean difference -10.16; 95% CI: -22.08 to 1.76) but lacked statistical significance (p=0.095). A similar favorable trend appeared in the nasal symptom subdomain (p=0.208). Per-protocol analysis demonstrated Xylitol significantly reduced endoscopic mucosal edema compared to saline at 4–6 weeks post-RT (p=0.047). No adverse events occurred. Conclusion: Xylitol nasal irrigation is a safe, beneficial adjunctive therapy that prevents symptom deterioration in NPC patients undergoing RT. Although the primary outcome narrowly missed statistical significance, likely due to sample size, xylitol significantly reduced mucosal edema in adherent patients.