Nanoparticles (NPs) are usually treated as multifunctional agents combining several therapeutical applications, like imaging and targeting delivery. However, clinical translation is still largely hindered by several factors, and the rapidly formed protein corona on the surface of NPs is one of them. The formation of protein corona is complicated and irreversible in the biological environment, and protein corona will redefine the “biological identity” of NPs, which will alter the following biological events and therapeutic efficacy. Current understanding of protein corona is still limited and incomplete, and in many cases, protein corona has adverse impacts on nanomedicine, for instance, losing targeting ability, activating the immune response, and rapid clearance. Due to the considerable role of protein corona in NPs’ biological fate, harnessing protein corona to achieve some therapeutic effects through various methods like biomimetic approaches is now treated as a promising way to meet the current challenges in nanomedicine such as poor pharmacokinetic properties, off-target effect, and immunogenicity. This review will first introduce the current understanding of protein corona and summarize the investigation process and technologies. Second, the strategies of harnessing protein corona with biomimetic approaches for nanomedicine design are reviewed. Finally, we discuss the challenges and future outlooks of biomimetic approaches to tune protein corona in nanomedicine.