Background and Objectives: Heart failure with reduced ejection fraction (HFrEF) remains a significant burden. Traditional herbal medicines have shown cardioprotective effects in treating HFrEF. However, the implications of herbal formulation considering the dynamic immunohistological changes in the myocardium following acute ischemic injury have been insufficiently discussed. This review investigated the efficacy and mechanisms reported in studies using rat or mouse models of HFrEF induced by left descending coronary artery ligation. Materials and Methods: A systematic search was conducted using PubMed, Embase, AMED, CINAHL, and CENTRAL databases. Information was extracted regarding study characteristics, disease model induction protocols, intervention characteristics, treatment protocols, outcomes, and suggested mechanisms. Hierarchical cluster analysis of test drugs was performed based on constituent herb similarities. The risk of bias (RoB) was assessed using the Systematic Review Center for Laboratory animal Experimentation RoB tool. Results: Overall, 26 studies met the eligibility criteria. HF model induction periods after LADCA ligation ranged from 1 day to 12 weeks. Most studies administered the test drug for four weeks. Commonly used herbs included Panax ginseng, Astragalus membranaceus, Salvia miltiorrhiza, Carthamus tinctorius, and Lepidium apetalum, which demonstrated anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through various signaling pathways. The overall RoB was relatively high. No significant association was found between model induction periods and herbal formulations or examined mechanisms. Conclusions: Future research should consider the time-dependent immunohistological features of the myocardium during HF treatment.