To investigate the effect of one-appointment root canal therapy on aesthetics and safety of patients with dental pulp disease. Methods A total of 90 patients with dental pulp disease admitted to our hospital from January 2022 to January 2023 were randomly divided into control group and study group, with 45 patients in each group. The control group was treated with multiple root canal therapy, and the study group was treated with one-appointment root canal therapy. The clinical efficacy, aesthetics, pain degree and complications were compared between the two groups. Results The total effective rate of treatment in the study group was 95.56%, which was higher than 77.78% in the control group (P <0.05). After treatment, the aesthetic score of the study group was higher than that of the control group, and the VAS score was lower than that of the control group (P <0.05). The incidence of complications in the study group was 4.44%, which was lower than 17.78% in the control group (P <0.05). Conclusion The application of one-appointment root canal therapy in patients with dental pulp disease is effective, which can improve the aesthetics of patients' teeth, reduce pain, and have fewer complications after treatment, with higher safety.