<p>This study aimed to develop a linezolid-loaded film-forming solution for treating diabetic foot ulcers, enhancing patient compliance and therapeutic efficacy. Linezolid was selected due to its antimicrobial properties, which aid in wound healing. To prevent drug interactions, topical film-forming solutions are derived from biodegradable polymers, such as chitosan. To prepare the 2% chitosan solution in 1% acetic acid for the FFS. The medication distribution was homogeneous, including linezolid, dissolved in ethanol and polyethene glycol 400 (PEG 400) as a plasticiser. The goal of this strategy was to provide a consistent supply of medication for effective infection control. Using design expert software, nine formulations (F1-F9) were developed, with F6 being optimised for its reduced drying time, low viscosity, and superior drug release. Zero-order linear drug release with sustained-release characteristics was shown in in vitro experiments. Comparing the optimised formulation group to a commercial product, animal tests demonstrated superior wound healing; a histo-morphological study showed less inflammation and increased epithelium regeneration. In conclusion, the optimised linezolid-loaded FFS presents a potentially effective therapeutic option for diabetic foot ulcers, improved healing, and continuous drug release. When used topically, it decreases medication interactions and increases patient compliance.</p> Graphical Abstract <p></p>