Atherosclerosis (AS) management typically relies on therapeutic drug interventions, but these strategies typically have drawbacks, including poor site specificity, high systemic intake, and undesired side effects. The field of cell membrane camouflaged biomimetic nanomedicine offers the potential to address these challenges thanks to its ability to mimic the natural properties of cell membranes that enable enhanced biocompatibility, prolonged blood circulation, targeted drug delivery, and evasion of immune recognition, ultimately leading to improved therapeutic outcomes and reduced side effects. In this study, a novel biomimetic approach was developed to construct the M1 macrophage membrane‐coated nanoprodrug (MM@CD‐PBA‐RVT) for AS management. The advanced MM@CD‐PBA‐RVT nanotherapeutics were proved to be effective in inhibiting macrophage phagocytosis and facilitating the cargo delivery to the activated endothelial cells of AS lesion both in vitro and in vivo. Over the 30‐day period of nanotherapy, MM@CD‐PBA‐RVT was capable of significantly inhibiting the progression of AS, while also maintaining a favorable safety profile. In conclusion, the biomimetic MM@CD‐PBA‐RVT showed promise as feasible drug delivery systems for safe and effective anti‐AS applications.This article is protected by copyright. All rights reserved