Objective: To assess periodontal tissue regeneration combined with orthodontics' effect on the inflammatory microenvironment, osteocalcin level, and masticatory function and stability of offending teeth in periodontitis as well as its overall clinical therapeutic effect. Methods: 80 patients with periodontitis treated in our hospital were enrolled and separated into observation group (n = 40) (periodontal tissue regeneration combined with orthodontic therapy) and control group (n = 40) (orthodontic therapy). All patients were followed up for 12 weeks. Inflammatory cytokines in the culture supernatant of periodontal cells and masticatory function of offending teeth in both groups after treatment were measured, and osteocalcin level and stability of offending teeth in both groups were evaluated before treatment, and at 2, 4, 8 and 12 weeks after treatment. Moreover, the overall therapeutic effects were recorded, such as tooth loosening, subjective symptoms and performing function. Results: At 12 weeks after treatment, the levels of TNF-alpha, IL-6 and IL-1 in observation group were significantly reduced compared to control group (p< 0.05), and the masticatory function of offending teeth was superior to control (p < 0.05). At 2, 4, 8 and 12 weeks after treatment, the osteocalcin level and stability of offending teeth in observation group were better (p < 0.05). In terms of overall therapeutic effect, observation group presented significantly lower proportion of tooth loosening and superior scores of subjective symptoms and performing function of offending teeth (p < 0.05). Conclusion: Periodontal tissue regeneration combined with orthodontic therapy can effectively reduce the local inflammation and improve the masticatory function of patients with periodontitis. At 2 weeks after treatment, the osteocalcin level and stability of offending teeth are significantly improved, with a satisfactory clinical therapeutic effect.