The efficacy and safety of Shengmai preparation combined with Western medicine (SMP–WM) to treat coronary heart disease (CHD) were reviewed. Twenty-five randomized controlled trials of SMP–WM treatment for CHD were retrieved from seven databases and other trial sources between their inception and April 10, 2021. The risk of bias domains was accessed by Cochrane Collaboration’s tool, and the data were statistically analyzed using RevMan 5.3 and Stata 12.0 software. The majority of included studies had a low or unclear risk of overall bias. Total mortality was not reduced (RR = 0.39, 95% CI: 0.13–1.19, [Formula: see text] = 0.10), but the cardiovascular events (RR = 0.35, 95% CI: 0.22–0.54, [Formula: see text] < 0.01), weekly frequency (SMD = −2.38, 95% CI: −2.89 – −1.88, [Formula: see text] < 0.01), and duration (SMD = −3.24, 95% CI: −3.76 – −2.71, [Formula: see text] < 0.01) of angina pectoris attacks were significantly decreased by SMP–WM. The SMP–WM combination exerted antiplatelet activity by reducing platelet adhesion (SMD = −0.97, 95% CI: −1.49 – −0.45, [Formula: see text] = 0.0003) and the platelet reactivity index (SMD = −1.75, 95% CI: −2.04 – −1.46, [Formula: see text] < 0.01). SMP–WM could protect endothelial function by increasing nitric oxide (SMD = 1.28, 95% CI: 0.54–2.02, [Formula: see text] < 0.01) and decreasing endothelin (SMD = −1.26, 95% CI: −1.85 – −0.66, [Formula: see text] < 0.01). The combination also improved hemorheology by reducing whole blood viscosity (SMD = −1.59, 95% CI: −2.32 – −0.85, [Formula: see text] < 0.01), plasma viscosity (SMD = −0.65, 95% CI: −0.86 – −0.45, [Formula: see text] < 0.01), and fibrinogen (SMD = −4.21, 95% CI: −4.58 – −3.83, [Formula: see text] < 0.01). The SMP–WM combination favorably impacts cardiovascular events, angina symptoms, endothelial function, platelet aggregation, and blood viscosity, with comparable safety to that of routine Western medicine. Further investigation is required to enhance the strength of the evidence.