Objective To evaluate the clinical efficacy of clarithromycin (CLM) in the adjuvant treatment of chronic periodontitis systematically, obtain reasonable conclusions through evidence-based medicine, and provide guidance for clinical rational drug use. Methods Literature about CLM in the adjuvant treatment of chronic periodontitis was searched in CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, PubMed, ScienceDirect, and Embase databases from inception to February 2019 using a computer. Meta-analysis was performed on the homogeneous study using RevMan 5.3 software after two independent reviewers screened the literature, evaluated the quality of the study, extracted the data, and evaluated the risk of bias in the included studies. Results Six randomized controlled trials were included in 316 subjects. The meta-analysis showed that compared with the scaling and root planning (SRP) group, the probing depth (PD) was reduced in patients with CLM and SRP [MD=-1.00, 95%CI (-1.55, -0.45), P=0.000 04]. Clinical attachment loss was obtained [MD=-0.03, 95%CI (0.43, 0.65), P<0.000 01], and the difference between the groups was statistically significant. The modified sulcus bleeding index (mSBI) was reduced [MD=-0.01, 95%CI (-0.14, 0.19), P=0.66]. No significant difference was observed between the groups, but the decrease in mSBI was more significant in CLM combined with SRP group. Conclusion CLM combined with subgingival SRP can achieve remarkable results in treating chronic periodontitist.