Objective To investigate the therapeutic effect of esomeprazole combined with mosapride in the treatment of patients with esophagitis. Methods A total of 109 patients with esophagitis who were treated at Chaoyang Second Hospital from January 2024 to September 2024 were randomly divided into an observation group (55 patients) and a control group (54 patients). The control group received omeprazole + domperidone + colloidal bismuth pectinate for treatment, while the observation group received esomeprazole + mosapride + colloidal bismuth pectinate. The clinical efficacy, esophageal motility indicators before and after treatment, pain, quality of life, and medication reactions were statistically analyzed and compared between the two groups. Results (1) The observation group demonstrated superior therapeutic effectiveness relative to the control cohort (P<0.05). (2) Initial assessments revealed comparable baseline measurements between groups regarding esophageal sphincter pressure metrics, supine reflux duration proportion, and upright reflux time percentage, with no statistically meaningful disparities (P>0.05). Following 8 weeks of therapeutic intervention, the observation group exhibited significantly greater enhancements in these physiological parameters compared to the control group (P<0.05). (3) Pretreatment evaluations showed equivalent visual analog scale (VAS) scores and quality of life (QOL) assessments across both groups (P>0.05). Subsequent analysis after the 8-week treatment regimen revealed statistically significant improvements in both pain perception (VAS) and life quality metrics (QOL) favoring the observation group (P<0.05). (4) Comparative safety analysis indicated that the observation group experienced fewer treatment-related adverse events than the control group (P<0.05). Conclusions The therapeutic use of esomeprazole in combination with mosapride demonstrates significant clinical benefits for esophagitis patients, including enhanced treatment efficacy and improved esophageal motor function parameters. This dual-drug regimen effectively alleviates discomfort symptoms and elevates quality of life metrics while maintaining an advantageous safety profile. Furthermore, this pharmacological strategy plays a crucial role in facilitating patient recovery progression, showing substantial clinical value in disease management.