In this research, a textile surface was modified by the sol–gel methodology with a new antimicrobial coating containing nanoparticles active against bacteria resistant to antibiotics. The effect of ultrasonic irradiation power (40 to 90 kHz), the concentration of reagents (nanoparticles, precursor and acids) and time (15 to 72 min) were investigated in relation to the structure, morphology and antimicrobial activity of coatings with zinc oxide nanoparticles. The relationship between the sonocatalytic performance and structure of the resultant modification was established by using various techniques, such as FTIR spectroscopy (FTIR) and scanning electron microscopy with an EDX detector (SEM-EDX), thin-layer chromatography (TLC) and antimicrobial effects were determined on selected model microorganisms. The homogeneity of layers with ZnO nanoparticles on samples was increased by increasing the ultrasonic irradiation power and time. The ultrasonic irradiation unify did not only unify both the structure and the morphology of samples, it also prevented the agglomeration of the nanoparticles. Moreover, under optimal conditions, an antimicrobial coating with ZnO nanoparticles, active against bacterial species S. aureus and E. coli was efficiently prepared. Results of the Time-kill methodology revieled excellent results starting after 6 hours of exposal to antimicrobialy functionalized cellulose polymer.