Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet.