The aim of this study is to investigate the effect of an edible saliva substitute, oral moisturizing jelly (OMJ), and a topical saliva gel (GC) on dry mouth, swallowing ability, and nutritional status in post-radiotherapy head and neck cancer patients. Methods Sixty-two post-radiation head and neck cancer patients with xerostomia completed a blinded randomized controlled trial. They were advised to swallow OMJ (n = 31) or apply GC orally (n = 31) for 2 months. Outcome measures were assessed at baseline, 1, and 2 months, including subjective and objective dry mouth (Challcombe) scores, subjective swallowing problem scores (EAT-10), water swallowing time, clinical nutritional status (PG-SGA), body weight, and dietary intake. Results After 1 and 2 months of interventions, subjective and objective dry mouth scores, subjective swallowing problem scores, swallowing times, and clinical nutritional status in both groups were significantly improved (p < 0.0001). Compared to GC, OMJ group had higher percent improvement in all outcome measures (p < 0.001) except swallowing time and clinical nutritional status. Interestingly, subjective dry mouth scores were significantly correlated with subjective swallowing problem scores (r = 0.5321, p < 0.0001). Conclusions Continuous uses of saliva substitutes (OMJ or GC) for at least a month improved signs and symptoms of dry mouth and enhanced swallowing ability. An edible saliva substitute was superior to a topical saliva gel for alleviating dry mouth and swallow problems. These lead to improved clinical nutritional status. Thus, palliation of dry mouth may be critical to support nutrition of post-radiotherapy head and neck cancer patients. Clinical trial registry Clinicaltrials.gov NCT03035825 Keywords Dysphagia. Xerostomia. Saliva substitute. Nutritional status. Head and neck cancer. Radiation therapy Abbreviations BIA Bioelectrical impedance assessment BMI Body mass index EAT-10 Eating Assessment Tool OMJ Oral moisturizing jelly PG-SGA Patient Generate-Subjective Global Assessment WST Water swallowing test Electronic supplementary material The online version of this article (