This study highlights recent advances in the synthesis of nanoconjugates based on gold (Au(III)) complex with a bioactive polymer bearing sulfonate groups called thiol-poly(sodium styrene sulfonate) (PolyNaSS-SH) with various molecular weights (5, 10, and 35 kDa). The three nanomaterials differ substantially in shape and structure. In particular, for PolyNaSS-SH of 35 kDa, we obtained a characteristic core−shell flower shape after chelation of the Au(III) ions and successively reduction with sodium borohydride (NaBH 4). The mechanism of formation of the hybrid nanoparticles (PolyNaSS-SH@AuNPs (35 kDa) and their interactions between plasmatic proteins (human serum albumin (HSA), collagen I (Col 1), and fibronectin (Fn)) were deeply studied from a chemical and physical point of view by using several analytical techniques such as Raman spectroscopy, UV−visible, transmission electron microscopy (TEM), 1 H NMR, and X-ray photoelectron spectroscopy (XPS).