To analyze the effect of combined periodontal-orthodontic treatment on patients with severe periodontal disease and malocclusion of anterior teeth. Methods A total of 76 patients with severe periodontal disease and malocclusion of anterior teeth admitted to Hunan Provincial People's Hospital from January 2020 to August 2022 were randomly divided into control group and experimental group, with 38 patients in each group. The control group was treated with periodontal basic treatment, and the experimental group was treated with periodontal-orthodontic combined treatment. The clinical efficacy, oral indicators, inflammatory factor levels and complications were compared between the two groups. Results The total effective rate of treatment in the experimental group was 97.37%, which was higher than 78.95% in the control group (P <0.05). After treatment, the gingival index, plaque index and gingival sulcus bleeding index in the experimental group were lower than those in the control group (P <0.05). After treatment, the levels of IL-8 and TNF-α in the experimental group were lower than those in the control group (P <0.05). There was no significant difference in the incidence of complications between the two groups (P >0.05). Conclusion Periodontal-orthodontic combined treatment has a good effect on severe periodontal disease with malocclusion of anterior teeth, which can improve the oral index of patients, reduce the level of inflammatory factors, and has fewer complications and higher safety.