Wound infections pose a significant challenge in healthcare settings due to prolonged healing times and the emergence of antibiotic-resistant bacteria. Traditional wound dressings often fail to provide sustained drug release, optimal moisture retention, and effective antibacterial protection, leading to suboptimal therapeutic outcomes. This study aimed to optimize and develop neomycin-integrated hydrogels crosslinked via tannic acid (TA) for the treatment of infectious wounds. The hydrogels were optimized using a central composite experimental design. The amounts of polyvinyl alcohol (PVA, 10-20% /) and polyvinylpyrrolidone (PVP, 5-20% /) were varied and mixed with a fixed concentration of TA (1% /) as a crosslinker. The water content (%), water absorption (%), erosion (%), water vapor transmission rate (WVTR), and the mechanical properties of the hydrogels were evaluated. Neomycin was integrated in the optimized hydrogel, and the antibacterial activity against Staphylococcus aureus was studied using a time-kill analysis method. The optimal hydrogel formula contained PVA and PVP at a ratio of 20:19.89 by weight. The resulting hydrogel possessed good physical and mechanical properties and had a water content of 71.86%, water absorption of 124.96%, minimal erosion of 33.08%, and optimal WVTR of 5567 g/m/24 h. Furthermore, the hydrogel showed desirable elasticity, with a Young's modulus of 474.81 Pa and a tensile strength that could resist breakage upon application. The neomycin-integrated hydrogels inhibited bacterial growth comparably to the neomycin solution (0.5% /). Therefore, TA was proven to be a promising natural crosslinker and the optimized hydrogel was demonstrated to be a propitious platform for neomycin cutaneous application, and which could be used to treat infected wounds in the future.