...Here, a biomimetic nanozyme (CuxO@EM-K) with augmented protein adsorption resistance, minimized immunogenicity, and enhanced biocompatibility is designed and synthesized. The CuxO@EM-K is made of CuxO nanozyme wrapped with modified 3xTg-AD mouse erythrocyte membrane with Aβ-targeting pentapeptide KLVFF. KLVFF serves as Aβ-specific ligand that works together with erythrocyte membrane to selectively capture Aβ in the blood. Meanwhile, the erythrocyte membrane coating prevents protein coronas formation and thus retains Aβ-targeting ability of CuxO@EM-K in biological fluids. More importantly, the CuxO core with multiple antioxidant enzyme-like activities stabilizes the outer erythrocyte membrane and simultaneously mitigates Aβ-induced membrane oxidative damage, which enables the extended systemic circulation indispensable for adsorbing Aβ. In vivo studies demonstrate that CuxO@EM-K not only reduces Aβ burden in the blood and brain but also ameliorates memory deficits in the widely used 3xTg-AD mouse model. Moreover, CuxO@EM-K shows no apparent toxicity in 3xTg-AD mice. Overall, this work provides an example for developing biocompatible and synergistic clearance of peripheral Aβ associated with AD.