The present study validated the cardioprotective effects of an in-house herbal medicine preparation BYDE in a mouse MI model, profiled 122 chemical compounds from BYDE by UPLC-MS/MS technology, predicted 37 proteins as the potential targets by network pharmacology analysis, and identified the preferable association with the TNF-α/NF-κB pathway. This evidence concerns the gene NFKB1 and myocardial infarction.