Atherosclerosis　(AS),　with　its　intricate　pathogenesis,　is　primarily　responsible　for　the　development　and　progression　of　cardiovascular　diseases.　Although　drug　development　has　made　some　achievements　in　AS　therapy,　limited　targeting　ability　and　rapid　blood　clearance　remain　great　challenges　for　achieving　superior　clinical　outcomes.　Herein,　ginsenoside　(Re)-　and　catalase　(CAT)-coloaded　porous　poly(lactic-coglycolic　acid)　(PLGA)　nanoparticles　(NPs)　were　prepared　and　then　surface　modified　with　U937　cell　membranes　(UCMs)　to　yield　a　dual　targeted　model　and　multimechanism　treatment　biomimetic　nanosystem　(Cat/Re@PLGA@UCM).　The　nanoparticles　consisted　of　a　core-shell　spherical　morphology　with　a　favorable　size　of　112.7　+/-　0.4　nm.　Furthermore,　UCM　assisted　the　nanosystem　in　escaping　macrophage　phagocytosis　and　targeting　atherosclerotic　plaques.　Meanwhile,　loading　with　catalase　might　not　only　exhibit　favorable　antioxidant　effects　but　also　enable　H2O2-responsive　drug　release　ability.　The　Cat/Re@PLGA@UCM　NPs　also　exhibited　outstanding　ROS　scavenging　properties,　downregulating　ICAM-1,　TNF-alpha　and　IL-1　beta,　while　preventing　angiogenesis　to　attenuate　the　progression　of　AS.　Moreover,　the　nanodrugs　displayed　2.7-fold　greater　efficiency　in　reducing　the　atherosclerotic　area　in　ApoE-/-　mouse　models　compared　to　free　Re.　Our　nanoformulation　also　displayed　excellent　biosafety　in　response　to　long-term　administration.　Overall,　our　study　demonstrated　the　superiority　of　UCM-coated　stimuli-responsive　nanodrugs　for　effective　and　safe　AS　therapy.