Orthopedic Device-Related Infections (ODRIs) are a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria [1]. Current treatments, based on antibiotic administration, have proven to be ineffective [2]. Consequently, there is a need for antibiotic-free alternatives [3]. Antimicrobial peptides (AMPs) are a promising solution due to their broad-spectrum of activity, high efficacy at very low concentrations, and low propensity to induce resistance [4]. We aim to develop a new AMP-based chitosan nanogel coating to prevent ODRIs. Chitosan was functionalized with norbornenes (NorChit) through the reaction with carbic anhydride [5]. Then, the cysteine-modified AMP Dhvar5 was covalently conjugated to NorChit (NorChit-Dhvar5), through a thiol-norbornene photoclick chemistry, under UV-photoactivation [5]. Characterization was done by Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance spectroscopy (NMR) analyses, and a successful functionalization of chitosan with norbornenes and posterior Dhvar5 immobilization was proved. For NorChit-Dhvar5 nanogels production, the NorChit-Dhvar5 solution (0.15% w/v) and Milli-Q water were injected separately into a microfluidic system with rates of 1 µL/min and 10 µL/min, respectively. The nanogels were characterized regarding size, concentration, shape, and charge, using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and Dynamic light scattering (DLS). The nanogels antibacterial properties were assessed in Phosphate Buffer (PBS) for 6 h, against four relevant microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and S. aureus methicillin-resistant (MRSA)), and in Muller-Hinton Broth (MHB), supplemented with human plasma (1% (v/v)), for 6 h and 24 h against MRSA. The obtained NorChit-Dhvar5 nanogels, presented a round-shaped, ~100 nm and positive charge, even after 8 months of storage in water. NorChit-Dhvar5 nanogels in a concentration of 10¹⁰ nanogels/mL in PBS were capable of reducing the initial inoculum of S. aureus by 99%, E. coli by 90%, P. aeruginosa by 99% and S. aureus MRSA by 90%. These results were corroborated by a 99 S. aureus MRSA reduction, after 24 h in medium. Overall, this strategy presents a high potential to prevent antibiotic-resistant infection in the context of ODRIs.