Keeping the native structure and activity of proteins, while adsorbed onto a nanoparticle surface, is one of the pre-requisites for the real biological applications of nanoparticles. However, this phenomenon is poorly understood because of the lack of in-depth knowledge on the structural orientation of the adsorbed protein, complex surface chemistry and morphology of the nanoparticle. In this study, we present quantitative information on the structure and the activity of a few major blood proteins when adsorbed onto different morphological and surface functionalized gold nanoparticles (GNPs). A profound effect of both the particle anisotropy and the surface ligands on the secondary structural change and consequently the activity of the proteins were observed. Furthermore, a prominent effect on the cell viability assay was also observed, when the MTT assay was performed using MDA-MB 231 cell lines.