Introduction Inflammation is a key driver of adverse outcomes in acute myocardial infarction (AMI), yet current western anti-inflammatory therapies are limited by their single-target nature and side effects. Traditional Chinese medicine (TCM), such as Tanhuo Decoction (THD), offers a multi-target, low-toxicity alternative.Methods In a randomized controlled trial, AMI patients with high inflammatory responses received either standard Western medicine (WM) alone or combined with THD for 3 days. Clinical outcomes and inflammatory markers were assessed, and proteomic and network pharmacology analyses were performed.Results The THD + WM group showed significant reductions in neutrophil counts and hs-CRP levels, along with improved creatinine clearance rate (CCR), compared to WM alone. Proteomic analysis revealed downregulation of pro-inflammatory proteins (PTX3, IL-18, TNFRSF11A) and upregulation of the anti-inflammatory IL1RL2. THD also modulated lipid metabolism and insulin sensitivity pathways.Discussions THD enhances the anti-inflammatory and metabolic benefits of standard AMI therapy through multi-target pathway regulation. These findings support its integration into modern cardiovascular care, particularly for patients with high inflammatory and metabolic risk.