Objective To analyze the effect and safety of minocycline combined with tinidazole in the treatment of chronic periodontitis. Methods A total of 98 patients with chronic periodontitis（98 patients, from November 22, 2016 to November 11, 2017） were enrolled in this study. The patients were treated with tinidazole and minocycline plus tinidazole respectively. The clinical data of periodontal related to the two groups were compared, and the status of gingival crevicular fluid-related inflammation and the incidence of adverse reactions were compared. Results The periodontal related clinical indexes, gingival crevicular fluid inflammation index in the observation group were compared with those in the control group（P〈0.05）. There was no difference in the incidence of adverse reactions between the two groups（P〈0.05）. Conclusion Minocycline combined with tinidazole is safe and effective in the treatment of chronic periodontitis.