Objective To explore the clinical effect of different filling methods in root canal therapy for patients with dental pulp disease. Methods Sixty patients with dental pulp disease admitted to the Department of Stomatology, Humen Hospital of Traditional Chinese Medicine, Dongguan City, from December 2021 to June 2022 were selected as the research objects. They were divided into control group and experimental group according to the random number table method, with 30 cases in each group. The control group was given root canal cold side tooth filling, and the experimental group was given hot gutta-percha filling. The filling effect, tooth pain, filling index, inflammatory factor level and complications were compared between the two groups. Results The proper filling rate of the experimental group was 90.00%, which was higher than 73.33% of the control group, and the difference was statistically significant (P <0.05). The VAS score of the experimental group was lower than that of the control group after treatment, and the difference was statistically significant (P <0.05). The filling time and filling area ratio of the experimental group were better than those of the control group, and the differences were statistically significant (P <0.05). After treatment, the levels of IL-6 and TNF-α in the experimental group were lower than those in the control group, and the differences were statistically significant (P <0.05). The incidence of complications in the experimental group was 3.33%, which was lower than 16.67% in the control group, and the difference was statistically significant (P <0.05). Conclusion In the clinical treatment of dental pulp disease, the filling effect of hot gutta-percha filling is better than that of root canal cold side tooth filling, which is helpful to improve the patient's tooth chewing function, relieve pain, effectively control the inflammatory reaction, and promote the rehabilitation of patients. It is worthy of clinical application.