Metal and metal oxide nanoparticles coated on textile fabrics have showed remarkable antibacterial characteristics, suggesting that they could be utilized to prevent the spread of the COVID-19 and reduce outbreaks. Textile materials, such as medical cloths and cleaning workers, could help to stop the spread of the COVID-19 Corona Virus in health institutions. Copper oxide nanoparticles (CuO-NPs) coated cotton/starched cotton, as well as their functionalized CuO–Ag nanocomposites and Cu(II)-curcumin complex, were synthesized in this study. CuO-NPs are less likely to leach when starched cotton materials are used instead of unstarched cotton. The none-toxic biocompatible starch material has improved the adhesion properties of the cotton fibers and enhanced its durability towards CuO-NPs. Deposition of CuO has improved by 39.5% after 3 wt% starch was used and its antimicrobial activity of CuO-coated cotton has increased by 50% for E. coli and by 23% for S. aureus. The functionalization of CuO-coated cotton with curcumin or Ag nanoparticles has enhanced the antimicrobial performance of the fabric because of the synergistic behavior of CuO, Ag, and curcumin. The results have showed excellent antimicrobial activity against E. coli and S. aureus. •CuO-NPs are coated in/onto the surface of cotton/starched cotton substrates via ultrasonic irradiation method.•The used of starch as none toxic material for coating cotton fibers is to improve the stability and enhance their durability.•The antimicrobial activity of CuO-NPs/starched cotton showed a remarkable enhancement than that of CuO-NPs/cotton.•The CuO–Ag and Cu(II)-curcumin complex/cotton showed much higher antimicrobial activity than CuO-NPs/cotton.