Objective To explore the application effect of different root canal filling methods in root canal therapy for patients with endodontic disease. Methods A total of 90 patients with endodontic disease who were treated in Linyi Yizhou Hospital from July 2022 to June 2023 were selected as the research objects. According to the random number table method, they were divided into reference group 1, reference group 2 and study group, with 30 patients in each group. The reference group 1 was filled with AH-plus warm gutta-percha vertical compaction, the reference group 2 was filled with AH-plus cold gutta-percha lateral compaction, and the study group was filled with iRootSP single point filling method. The masticatory function, periodontal health level, inflammatory factor level, pain degree and complications of the three groups were compared. Results After treatment, the bite force and masticatory efficiency of the study group were higher than those of the reference group 1 and the reference group 2, and the gingival index, bleeding index, looseness, VAS score, TNF-α, IL-6, hs-CRP and complication rate were lower than those of the reference group 1 and the reference group 2 (P <0.05). Conclusion In the root canal treatment of patients with endodontic disease, iRootSP single point filling can effectively restore the occlusal and masticatory function of patients, inhibit the level of inflammatory factors, reduce the degree of pain, and the risk of complications during treatment is lower.