Objective: To observe the effects of He-Ne laser irradiation combined with proton pump inhibitors (PPIs), gastric motility drug on reflux esophagitis. Methods: 126 RE patients were randomly divided into observation group and control group, with 63 cases each. The control group was treated with itopril and esomeprazole, the observation group was treated with laser irradiation on the basis of the control group. The differences of clinical efficacy, clinical symptom score, endoscopic grading score, esophageal dynamics indexes, the levels of gastrointestinal hormones and pepsinogens before and after treatment were compared between the two groups. Results: The total effective rate of the observation group (92.06%) was significantly higher than that of the control group (77.78%), and the difference was statistically significant (P<0.05). After treatment, clinical symptom scores such as heartburn, acid reflux, chest pain and endoscopic grading scores in both groups reduced (P<0.05), but compared with the control group, the clinical symptom scores and endoscopic grading scores of the observation group reduced significantly (P<0.05). After treatment, the pressure of esophageal sphincter was significantly increased in the two groups, and the vertical reflux time ratio, horizontal reflux time ratio and total reflux time ratio were significantly decreased (P<0.05), but the improvement degree of the above indicators in the observation group was greater than that in the control group (P<0.05). Compared with before treatment, GAS, MOT, PG Ⅰ, PG Ⅰ/PG Ⅱ after treatment significantly increased in the two groups (P<0.05), VIP decreased obviously (P<0.05), but the improvement of the above indexes in the observation group was greater than that in the control group (P<0.05).Conclusion: He-Ne laser irradiation combined with PPIs, gastric motility drug have a significant effect on RE, which is better than PPIs combined with gastric motility drug, and can effectively improve the esophageal dynamics and gastrointestinal hormone levels of the patients.