Objective To compare the effects of iRoot SP cold lateral condensation method and warm gutta-percha vertical condensation method in root canal treatment of dental pulp disease. Methods A total of 100 patients with dental pulp disease who underwent root canal treatment in Yancheng Stomatological Hospital from January 2023 to January 2024 were selected, and they were divided into the control group and the observation group according to different root canal filling methods, with 50 patients in each group. The control group was filled with warm gutta-percha vertical condensation method, and the observation group was filled with iRoot SP cold lateral condensation method. The root canal filling effect, pain degree, masticatory function and adverse reactions were compared between the two groups. Results The obturation rate of the observation group was higher than that of the control group, while the overfilling rate and underfilling rate were lower than those of the control group (P<0.05). The VAS scores of the observation group at 1 day and 1 week after treatment were lower than those of the control group (P<0.05). The occlusal force and masticatory efficiency of both groups at 3 months after treatment were higher than those before treatment, and those of the observation group were higher than those of the control group (P<0.05). The incidence of periapical inflammation and tooth fracture in the observation group was lower than that in the control group, but the difference was not statistically significant (P>0.05). Conclusion The application effect of iRoot SP cold lateral condensation method in root canal treatment of dental pulp disease is better than that of warm gutta-percha vertical condensation method. It has better filling effect, can effectively relieve pain, promote the recovery of masticatory function, and does not increase the incidence of periapical inflammation and tooth fracture after treatment, with higher application safety.