The enhanced antioxidant activity of surface-functionalized gold nanoparticles (AuNPs) synthesized by self-assembly has attracted great attention, but little is known about the mechanism behind the enhanced activity. To address this challenge, the antioxidant activity of Au@PEG3SA (i.e., surface-functionalization of spherical AuNPs with the antioxidant salvianic acid A) was used as an example to illustrate the mechanism of the enhanced activity. Evaluation of the antioxidant activity was performed in a radical-scavenging reaction between Au@PEG3SA and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. As expected, the rate constant for the reaction of Au@PEG3SA with DPPH was about nine times greater than that for the salvianic acid A monomer. A comparative analysis of the spectral characteristics of Au@PEG3SA and the salvianic acid A monomer further imply that the enhancement of the antioxidative reaction kinetics may be ascribed to the variation in the transition state for the DPPH-radical scavenging reaction through π–π stacking interactions between and among adjacent groups on the surface of Au@PEG3SA. On the other hand, the kinetic enhancement of Au@PEG3SA on reactive-oxygen-species (ROS) scavenging can be observed in living cells and in vivo, which possibly provides new insight for the bioapplication of self-assembly of surface-functionalized AuNPs.