Several selected studies dealing with the development of novel antimicrobial metal oxide-coated cotton nanocomposites and their antimicrobial applications have been reviewed in this chapter. Synthesis of metal oxide nanoparticles (NPs) and its deposition onto cotton fibers were conducted using various methods. These include the high energy γ-radiation, thermal treatment-assisted impregnation, "pad-dry-cure" of the impregnated fabric in the colloid formulation of metal oxide soluble, and ultrasonic radiation methods. The coated metal oxide nanoparticles have shown an effective enhancement for antimicrobial activity. They reduce the chance of diseases originating from hospital infections. The antimicrobial properties of cotton fabrics finished with metal oxide NPs against a variety of bacterial strains commonly associated with nosocomial infections, caused by Staphylococcus aureus and Escherichia coli, have been investigated by four different methods. The morphology of the cottoncoated metal oxide nanoparticles and their chemical structure have been analyzed by UV-vis, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectra (XPS). SEM and XRD analyses revealed that the shape and size of the coated nanoparticles are dependent on the nature of the metal oxide and its preparation conditions.