This study presents a novel, biodegradable and biocompatible levofloxacin (LVX) release system based on metal-organic frameworks (MOF) and silk. The synergic effect between the silk fibroin and metal-organic frameworks not only provides the matrix for the efficient MOF distribution but, above all, builds an innovative composite material that may be used as a nanocomposite fibre building patients’ hospital clothes and healthcare employees’ uniforms against nosocomial infections and pathogens. In this study, a series of composite zirconium-based MOFs, varied in terms of the defectivity and the presence of functional groups and silk fibroin were tested in terms of LVX release kinetics, biocompatibility and biocidal activity towards all reference Gram-positive and Gram-negative bacteria. The obtained materials were characterized by using various characterization techniques including low-temperature N2 adsorption, scanning electron microscopy, optical microscopy and Fourier Transforms Infrared spectroscopies, and DFT modelling. The results indicate that the developed LVX@UiO-66 25 % HCl@SILK sponge composite material possesses high biocidal activity toward Gram-positive and Gram-negative bacteria. Additionally, in vivo experiments have indicated that developed material may be considered potentially safe for living organisms.