Objective To explore the effect of orthodontics combined with prosthodontic treatment on periodontal health indicators and occlusal function in patients with dentition defect. Methods A total of 60 patients with dentition defect admitted to the Department of Stomatology, Hai'an People's Hospital from January 2023 to January 2024 were selected. According to the random number table method, they were divided into the control group and the observation group, with 30 patients in each group. The control group received conventional denture restoration, and the observation group received orthodontics combined with prosthodontic treatment. The clinical efffcacy, occlusal function, periodontal health indicators, aesthetic effect, quality of life and adverse reaction rate were compared between the two groups. Results The total effective rate of treatment in the observation group (96.67%) was higher than that in the control group (80.00%) (P<0.05). After treatment, the occlusal force and masticatory efffciency in the observation group were higher than those in the control group, and the levels of PLI, PD and SBI were lower than those in the control group (P<0.05). After treatment, the aesthetic score of the observation group was higher than that of the control group, and the OHIP-14 score was lower than that of the control group (P<0.05). The incidence of adverse reactions in the observation group (6.67%) was lower than that in the control group (26.67%) (P<0.05). Conclusion For patients with dentition defect, orthodontics combined with prosthodontic treatment can effectively improve clinical efffcacy, occlusal function and periodontal health status, enhance aesthetic effect and oral quality of life, with favorable safety.