The development of multifunctional cotton fabrics that are stain-resistant, antimicrobial, and easy to clean has sparked scientific interest as well as practical usefulness, owing to its medical and healthcare applications. The purpose of this study was to fabricate self-cleaning and antimicrobial cotton for final use by soaking the cotton fabric in nonfluorinated hybrid formulations based on quaternary chitosan-silane using the sol-gel process. The fluorine-free cotton fabric demonstrated high self-cleaning behavior and outstanding bacterial killing efficacy against E. coli and S. aureus bacteria, without altering the desired textile properties of cotton fabric. Remarkably, cotton textiles using the hybrid formulations HTACC-VTES (N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride-vinyltriethoxy silane) and TMCC-VTES (N, N, N-trimethyl chitosan chloride-vinyltriethoxy silane) demonstrated promising water contact angles of 147° and 142° respectively, indicating a move toward superhydrophobicity. In FTIR spectra, both treated cotton textiles had an absorption peak at 1208 cm-1 (SiOC bending), indicating a stronger interaction between silane binding agents and the cotton substrate. The treated cotton fabric with desirable features retains its stability and endurance after 12 cycles of washing for antibacterial tests and 15 cycles for wettability tests. The manufactured cotton fabric has several potential applications, such as in personal hygiene items and medical applications.