Various polymer brushes with linear and looped conformations have gained considerable attention in the application of biomaterials and nanotechnology. In this work, the linear and looped polymer brush shells based on PEG-SH and SH-PEG-SH chains binding to gold nanoparticles (AuNPs) are synthesized. The structure and topology of the PEGylated AuNPs are systematically investigated. The basic physicochemical parameters of these PEGylated AuNPs such as hydrodynamic size, grafting density, hydrophilicity, colloidal stability, and biocompatibility are determined intensively. The looped polymer topology can remarkably alter physicochemical properties of polymer brushes compared with the linear counterparts. When the molecular weight of PEG is low (1 and 5 kDa), the looped polymer shells have smaller hydrodynamic size and lower grafting density than their linear analogues; when the molecular weight of PEG is high (10 kDa), the looped shells are much thicker and denser than the linear ones. Interestingly, the looped PEGs on AuNPs are more stable in a high-salt environment and have better hydrophilicity, which endow excellent biocompatibility, including protein resistance and cell viability. These results provide a simple approach to design polymer brushes with different topologies on AuNPs, improve the biocompatibility of hybrid AuNPs, and acquire the potential application in the biomedical field.