Coronary artery disease (CAD) is defined as one of the most common cardiovascular diseases (CVDs). Periodontitis is one of the risk factors for CAD. PubMed, Embase and Cochrane Library databases were carefully and thoroughly retrieved until October 2021. On the basis of the inclusion and exclusion criteria, eligible articles were selected strictly to identify randomized controlled trials (RCTs). Using Cochran's Q statistic, Review Manager 5.4 and Stata 16, data were extracted, and a comprehensive analysis was carried out. Six RCTs of 619 patients were included in this study, including 360 in the intervention group (IG) and 259 in the control group (CG). Meta-analysis showed significant difference for C-reactive protein (CRP) (1.20mg/L, 95% CI: 1.13 to 1.27, p < 0.00001) after non-surgical periodontal therapy (NSPT), but showed no significant difference for interleukin-6 (IL-6) (1.19mg/L, 95% CI: -1.03 to 3.40, p=0.29), flow-mediated dilation (FMD) (-1.64%, 95% CI: -4.95 to 1.67, p=0.33), triacylglycerol (TG) (-0.02mg/dL, 95% CI: -0.31 to 0.27, p=0.90), total cholesterol (TC) (0.04mg/dL, 95% CI: -0.25 to 0.33, p=0.90), low-density lipoprotein cholesterol (LDL-C) (0.00mg/dL, 95% CI: -0.29 to 0.29, p=0.99) and high-density lipoprotein cholesterol (HDL-C) (0.11mg/dL, 95% CI: -0.18 to 0.40, p=0.46). The impact of NSPT on the reduction of CRP in patients of CAD with periodontitis is significant. NSPT can be considered as an important preventive strategy for major cardiovascular events in CAD.