This study investigated the molecular mechanisms underlying the therapeutic effects of ginsenoside Rh2 (G-Rh2) in coronary heart disease (CHD) through a network pharmacology approach, focusing on identifying key targets and pathways, including those involved in lipid metabolism, metabolism regulation and anti-apoptotic signaling. A multi-target network pharmacology analysis was performed to predict the pharmacoloigical targets and pathways of G-Rh2. Key molecular interactions were validated by molecular docking. In vivo experiments using CHD rat models were conducted to verify and quantify the effects of G-Rh2 on lipid profiles, myocardial pathology, and gut microbiota composition. G-Rh2 significantly ameliorated CHD in rats by reducing serum cholesterol and triglycerides levels, alleviating myocardial fibrosis, suppressing cardiomyocyte apoptosis, and mitigating tissue damage. Mechanistically, G-Rh2 activated the PI3K/AKT signaling pathway, regulated atherosclerosis-associated metabolic pathways (e.g., pentose phosphate and carbon metabolism), and modulated gut microbiota composition by reducing the abundance of harmful bacteria and increasing beneficial microbial populations, thereby enhancing lipid metabolism and energy balance. This study demonstrates that G-Rh2 alleviates CHD through the synergistic activation of the PI3K/AKT pathway, modulation of key metabolic pathways, and restructuring of gut microbiota. These findings underscore the potential of G-Rh2 as a multi-target therapeutic agent for CHD, offering mechanistic insights into its cardioprotective properties and supporting the broader application of G-Rh2 in cardiovascular drug development.