Atherosclerosis, a major cause of cardiovascular diseases, involves complex pathophysiological processes. The co-delivery of multiple bioactive components derived from phytomedicine to atherosclerotic plaque is challenging, especially for those with varied solubilities. This study introduces a novel metal-phenolic network-based core-shell recombinant high-density lipoprotein nanocarrier (SSPH-MPN@rHDL) for co-delivering multiple bioactive components from Salvia miltiorrhiza and Carthamus tinctorius, including salvianic acid A (SAA), salvianolic acid B (SAB), protocatechuic aldehyde (PCA), hydroxysafflor yellow A (HSYA), and tanshinone IIA (TS-IIA). These components have varied solubilities, presenting challenges for achieving synergistic therapeutic effects. The SSPH-MPN@rHDL system encapsulates the four hydrophilic components (i.e. SAA, SAB, PCA, HSYA) within a quaternary metal-phenolic network and a hydrophobic component (i.e. TS-IIA) in an outer lipid layer, facilitating targeted plaque delivery. In vitro and in vivo experimental results demonstrated that SSPH-MPN@rHDL enhanced anti-atherosclerotic efficacy through combined antioxidant, anti-inflammatory, and lipid-lowering actions. This approach offers new perspectives on using nanotechnology to optimize the delivery of phytomedicinal compounds for cardiovascular therapy.