<p>Au/Nd₂O₃ nanocomposites (NCs) have potential applications in nanomedicine due to their unique physicochemical properties. The interaction of biomacromolecules with NCs, known as protein corona (PC) formation, is influenced by the surface characteristics, which in turn depend on the synthesis method. In this study, Au/Nd₂O₃NCs were synthesized using both phytochemical (<i>Myrtus communis</i> extract) and chemical methods, and XRD, SEM, EDX, DLS, and FTIR were used to characterize their physicochemical properties. The NCs were analyzed with and without protein corona formation after exposure to healthy human plasma using SDS-PAGE and DLS. Results showed that protein corona formation reduced the hydrodynamic size and enhanced the stability of NCs. SDS-PAGE revealed differences in protein composition between NCs synthesized by the two methods, likely due to variations in surface chemistry and lattice parameters. Phytochemically synthesized NCs exhibited higher cellular internalization compared to chemically synthesized NCs, while MTT assays indicated minimal cytotoxicity in MDA-MB-231 and RAW264.7 cell lines, even at concentrations up to 200&#xa0;µg/mL, regardless of protein corona formation. The results demonstrate that the synthesis route significantly influences protein corona formation and cellular interactions. Moreover, phytochemically synthesized Au/Nd₂O₃ NCs exhibited high stability and low toxicity, underscoring their potential for biomedical applications.</p> Graphical abstract <p></p>