For the biomedical application of nanoparticles (NPs) it is necessary to know the mechanism of their interaction with biological systems. This work was focused on the interactions of NPs with proteins, which lead to the formation of a protein layer on the surface of NPs so called protein corona which significantly affects both the properties of NPs and the biological system. In previous studies of nano-bio interactions, the role of glycans, which are present in the structure of most proteins, has been neglected. The aim of the study was to determine how the size, shape and surface structure of silver and gold NPs affect the nature and mechanism of their interaction with proteins of different glycosylation status using models of glycosylated transferrin (glycoTRF) from human serum and non-glycosylated recombinant human transferrin (non-glycoTRF). The influence of physicochemical properties of NPs on the strength of protein binding, changes in the secondary structures of proteins and the composition of the protein corona was investigated. The study was also performed on bovine serum albumin (BSA) so that the obtained results could be compared with other studies that mainly use the BSA model.The ionic strength and pH of the biological medium significantly affected the colloidal stability of NPs whereas the formation of the protein corona stabilized them. It was found that the strength of protein binding to NPs and changes in secondary protein structure depend not only on the size, shape and surface functionalization of NPs, but also on the presence of glycans on proteins. The structure of -plates changed significantly by binding non-glycoTRF to NPs of less specific surface area, which was not observed for glycoTRF. Physicochemical properties of NPs and glycosylation of proteins also affected the composition and concentration of protein corona on the surface of NPs . The obtained results emphasize the importance of protein glycosylation for nano-bio interactions, which together with the confirmed role of physicochemical properties of NPs on these interactions, contributes to understanding the effect of NPs on biological systems and can be used in the development of new diagnostic, prognostic and therapeutic nanotools.