Objective: To explore the impact of health education based on self-care theory in reagard to the self-care ability of patients with peptic ulcer disease (PUD). Methods: This study was performed in 152 patients who were diagnosed with PUD at the digestive endoscopy center of People's Hospital of Rizhao from February 2018 to December 2019. These patients were randomly assigned to the experimental group and the control group (76 patients in each group). Patients in the experimental group received health education based on self-care theory. On the 15th and 30th days of intervention, telephone follow-up was completed to provide further nursing guidance. Patients in the control group received routine nursing guidance. On the 45th day after intervention, self-care ability and self-efficacy were comprehensively investigated and analyzed, while anxiety, social support, and Helicobacter pylori (HP) infection were briefly investigated and analyzed. Results: Self-care ability in the experimental group after intervention was significantly improved when compared with that before intervention, while the level of social support, relief of anxiety, and self-efficacy in the experimental group were significantly better than those in the control group (all P<0.05). Compared with that before intervention, the rate of HP infection in the experimental group after intervention was significantly reduced (P<0.05). Conclusion: Health education contributes to the improvement of self-care ability and reduction in the rate of HP infection in patients with PUD.