Myocardial injury is frequently associated with an exacerbated cardiac-specific inflammatory response, leading to an imbalance in immune micro environment homeostasis. T cells and macrophages recruited to the site of injury constitute the primary components of inflammatory infiltration. Both the polarization status of macrophages and the differentiation levels of inflammatory T cells exhibit plasticity, transitioning from pro-inflammatory to anti-inflammatory phenotypes during the disease course. However, under conditions of intensified inflammation and immune dysregulation, a persistent pro-inflammatory state is maintained, characterized by M1 macrophages and helper T cell 1 (Th1)/Th17/Th22 cells, along with group 3 innate lymphoid cells (ILC3s). Salidroside (SAL) exerts antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic effects on cardiomyocytes. This review aims to analyze the mechanism by which the single molecule SAL simultaneously reprograms the crosstalk balance between the three key cellular components (macrophages-T cells-cardiomyocytes) within the inflammatory microenvironment. Furthermore, it summarizes SAL’s mechanism of alleviating myocardial immune imbalance and associated inflammatory injury. This is achieved through blockade of the signal transducer and activator of transcription 3 (STAT3)/Th17/Interleukin-22 through type 2 cytokine receptor complex(IL-22-IL-22R) pro-inflammatory axis, promotion of macrophage polarization towards an anti-inflammatory phenotype, and modulation of T cell differentiation.