Objective To explore the application effect of the combination of mechanical nickel-titanium files and ultrasonic root canal therapy device in the root canal treatment of deciduous dental pulp disease. Method A total of 186 children with deciduous dental pulp disease treated in the Department of Stomatology, Suiyang District Maternal and Child Health Hospital, Shangqiu City from March 2023 to October 2024 were randomly divided into a study group of 93 cases and a control group of 93 cases. The control group received traditional manual K-files during root canal treatment, while the study group received mechanical nickel titanium files and ultrasonic root canal therapy. The treatment process time, root canal filling effect, pain situation [Wong-Baker FACES pain rating scale (WBFPS)], gingival crevicular fluid inflammatory factor levels[interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], complications, and 6-month postoperative treatment success rate were compared between the two groups. Results The study group demonstrated higher root canal filling rates and treatment success rates compared to the control group, with significantly shorter root canal preparation time, total root canal treatment duration, and lower complication rates (all P＜ 0.05). Postoperative WBFPS scores at 24 h and 7 d, as well as gingival sulcus fluid levels of IL-1β, IL-6, and TNF-α, were significantly lower in the study group than preoperative values. Furthermore, all postoperative scores and gingival sulcus fluid parameters in the study group were statistically inferior to those in the control group (all P＜0.05). Conclusion The combined use of mechanical nickel-titanium files and ultrasonic root canal therapy devices in the treatment of deciduous dental pulp disease can effectively reduce treatment time, minimize postoperative inflammation, pain, and complications, while improving root canal filling efficacy and treatment success rates.