Schisandra chinensis is a commonly used traditional Chinese medicine, which has been widely used in the treatment of acute myocardial infarction in China. However, it has been difficult to systematically clarify the major pharmacological effect of Schisandra, due to its multi-component complex mechanism. In order to solve this problem, a comprehensive network analysis method was established based-on “component– gene ontology–effect” interactions. Through the network analysis, reduction of cardiac preload and myocardial contractility was shown to be the major effect of Schisandra components, which was further experimentally validated. In addition, the expression of NCOR2 and NFAT in myocyte were experimentally confirmed to be associated with Schisandra in the treatment of AMI, which may be responsible for the preservation effect of myocardial contractility. In conclusion, the three-mode gene ontology network can be an effective network analysis workflow to evaluate the pharmacological effects of a multi-drug complex system.