Objective To study the clinical effect and safety of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Methods A total of 50 patients with chronic periodontitis admitted to Mudu Hailong Dental Clinic in Wuzhong District from January 2021 to June 2022 were selected as the research objects. They were divided into control group and observation group by random number table method, with 25 cases in each group. The control group was treated with tinidazole, and the observation group was treated with tinidazole combined with minocycline hydrochloride ointment. The clinical efficacy, periodontal indexes [plaque index (PLI), gingival sulcus bleeding index (SBI), periodontal pocket depth (PPD)] and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 96.00%, which was higher than 76.00% in the control group, and the difference was statistically significant (P0.05). Conclusion For patients with chronic periodontitis, minocycline hydrochloride ointment combined with tinidazole can effectively improve the periodontal condition, and will not increase the incidence of adverse reactions, with good efficacy, which is worthy of promotion and application.