Three types of precursor microparticles based on glycidyl methacrylate, hydroxyethyl methacrylate and one of the following three crosslinking agents (mono-, di- or triethylene glycol dimethacrylate) were prepared using the suspension polymerization technique. The precursor microparticles were subsequently used to obtain three types of hybrid microparticles. Their synthesis took place by grafting sodium hyaluronate, in a basic medium, to the epoxy groups located on the surface of the precursor microparticles. Both types of the microparticles were characterized by: FTIR spectroscopy, epoxy groups content, thermogravimetric analysis, dimensional analysis, grafting degree of sodium hyaluronate, SEM and AFM analyses, and specific parameters of porous structures (specific surface area, pore volume, porosity). The results showed that the hybrid microparticles present higher specific surface areas, higher swelling capacities as well as higher adsorption capacities of antimicrobial drugs (metronidazole). To examine the interactions between metronidazole and the precursor/hybrid microparticles the adsorption equilibrium, kinetic and thermodynamic studies were carried out. Thus, it was determined the performance of the polymer systems in order to select a polymer–drug system with a high efficiency. The release kinetics reflect that the release mechanism of metronidazole in the case of hybrid microparticles is a complex mechanism characteristic of anomalous or non-Fickian diffusion.