Stable hydrophilic and protein‐repellent surfaces from nontoxic polysaccharides are highly desirable in several biomedical applications such as implants and prosthetics. Herein, a water‐based one‐step strategy to functionalize polydimethylsiloxane (PDMS) surfaces with chitosan‐based bioparticles is described to suppress the adsorption of blood plasma proteins, which causes biofilm formation and implant‐associated infection. Micro‐ and nanosized chitosan (Chi) and carboxymethyl chitosan (CMChi) particles, featuring high stability, hydrophilicity, and zwitterionic feature, are synthesized in an ecofriendly solvent water and their interaction with PDMS surfaces is investigated in‐real time over a wide range of pH (3–10) using a quartz crystal microbalance with dissipation (QCM‐D). The results show that both Chi and CMChi form stable colloidal particles at pH close to their zero‐point charge, and thus exhibit maximum adsorption and irreversibly bound layers on PDMS surfaces. Coating from CMChi shows high stability, improved hydrophilicity, and subsequently no adsorption of bovine serum albumin and enhanced resistance to fibrinogen, compared to Chi and native PDMS, as revealed by water contact angle and QCM‐D measurements. The results demonstrate the possibility to develop novel and biobased coating materials to address unspecific protein adsorption not only on silicone‐based implants but also on other biomaterials in general.