Macrophages, along with the inflammatory and maladaptive immune responses they trigger, play crucial roles in the progression and rupture of atherosclerosis. We develop an adaptable platelet-protein platform tailored for the targeted delivery of both antioxidant nanocatalysts and TRAF6 inhibitor to advance synergistic therapy for atherosclerosis. The platform is constructed by assembling nanocatalyst- and TRAF6 inhibitor-loaded protein clusters with reactive oxygen species-cleavable linkers, then anchoring them onto the platelet surface for guided delivery to atherosclerotic plaques. Upon entering the reactive oxygen species-rich microenvironment, the platform disintegrates into ultra-small protein blocks, facilitating plaque penetration and selective macrophage internalization. The Mn-based nanocatalyst effectively scavenges various reactive oxygen species, while Mn ions concurrently enhance T1-weighted magnetic resonance imaging signals for diagnosis of atherosclerotic plaques. Meanwhile, the TRAF6 inhibitor blocks macrophage activation mediated by T lymphocytes. In a male mouse model of atherosclerosis, the versatile platform integrates cell-mediated natural targeting with adaptable size transformation for enhanced intraplaque penetration and unfavorable macrophage signaling reprogramming, offering opportunities for precise and multifaceted atherosclerosis therapy.