Matrine (MAT) is a natural alkaloid extracted from the traditional Chinese herb Sophora flavescens, combining the natural attributes of herbal medicine with the well-defined efficacy advantages of chemical drugs. It exerts broad regulatory effects in areas such as anti-inflammation, endothelial cell (EC) function protection, and phenotypic switching of vascular smooth muscle cells (VSMC). In recent years, MAT has attracted extensive attention in the field of vascular remodeling due to its multi-targeted regulatory properties. Research indicates that MAT participates in the onset and progression of various vascular remodeling-related diseases, including atherosclerosis (As), angiogenesis, and pulmonary hypertension (PH). Its mechanisms involve improving vascular endothelial cell (EC) dysfunction, regulating the phenotypic switching of VSMC, and inhibiting the abnormal activation and chemotaxis of monocytes/macrophages. This article systematically reviews the mechanisms of MAT in vascular remodeling. Based on this evidence, the application of MAT holds promise as a new direction for future clinical therapies.