For the time being, a great attention has been given to the search of green and reusable materials with antibacterial properties. The present research focused on the design and synthesis of hybrid structures constituting superparamagnetic iron oxide nanoparticles (SPIONs) coated with sugar ligands (SL), synthesized using a green and efficient microwave (MW)-assisted hydrothermal synthesis. The sugar ligands were selectively engineered to obtain antibacterial characteristics towards multi-drug resistant bacterial strains, which are among the most problematic bacterial species in antibiotic development efforts. The superparamagnetic behavior was obtained by synthesizing core iron oxide nanoparticles with a diameter below twenty nm. The MW-assisted hydrothermal method yielded a uniform coating of SPIONs with several sugar ligands, granting strongly negative-charged surfaces, which have eventually contributed to their bactericidal activity. The research work allowed to get insights into the magnetic properties of the sugar ligand coated SPIONs, as well as on morphological and functional characteristics of the hybrid nanoparticles, by employing both spectroscopy and imaging techniques, such as FT-IR, Scanning/Transmission Electron Microscopy (S/TEM). Detailed characterizations of the nanoparticles' charge, using zeta potential analysis helped to identify the highly charged hybrids for antibacterial applications. Furthermore, studies on the bactericidal properties of selected SL-SPION hybrids highlighted a high selectivity towards both gram-negative and gram-positive bacteria along with improving bactericidal activity of streptomycin/penicillin mixture. Detailed studies done on Pseudomonas aeruginosa revealed that the SPIONs selectively downregulated the virulence factor pyoverdine and altered bacterial morphology depending on the SL chemistry. The synthesized materials with antibacterial activity pave the way for an effective path towards the design and development of nanostructures and coatings against antibiotic-resistant bacterial species.