Introduction: Xerostomia (dry mouth) is a common side effect among patients with cancer undergoing chemotherapy. There is no standard treatment for this symptom yet, although Persian medicine textbooks suggested some products to relieve xerostomia. We aimed to assess the efficacy of honey-lime spray in treating chemotherapy-induced xerostomia in breast cancer patients through a controlled study. Methods: In this pilot, randomized, double-blinded clinical trial conducted in Shohadaye Tajrish Hospital, Iran, the intervention group received honey-lime spray and nystatin, while the control group used distilled water plus nystatin for 2 weeks. The six-item dry mouth form and visual analog score (VAS) were used to evaluate xerostomia extent and pain, respectively. Results: The standardized value of the difference between the mean scores before and after the study was −10.21 (p < 0.001), and the effect size was estimated at 55%. Also, VAS showed a significant decrease in pain for the intervention group compared with the control group (p < 0.001). There were no serious side effects. Conclusion: Honey-lime spray may be a good treatment choice for xerostomia in chemotherapy-induced breast cancer patients, but robust trials with larger samples and prolonged follow-ups are highly recommended.