Composites of Ag and TiO2nanoparticles were synthesized in situ on cotton fabrics using sonochemical and solvothermal methods achieving the successive formation of Ag-NPs and Ti-NPs directly on the fabric. The impregnated fabrics were characterized using ATR-FTIR spectroscopy; high-resolution microscopy (HREM); scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS); Raman, photoluminescence, UV-Vis, and DRS spectroscopies; and by tensile tension tests. Results showed the successful formation and impregnation of NPs on the cotton fabric, with negligible leaching of NPs after several washing cycles. The photocatalytic activity of supported NPs was assessed by the degradation of methyl blue dye (MB) under solar and UV irradiation revealing improved photocatalytic activity of the Ag–TiO2/cotton composites due to a synergy of both Ag and TiO2nanoparticles. This behavior is attributed to a diminished electron–hole recombination effect in the Ag–TiO2/cotton samples. The biocide activity of these composites on the growth inhibition ofStaphylococcus aureus(Gram+) andEscherichia coli(Gram−) was confirmed, revealing interesting possibilities for the utilization of the functionalized cotton fabric as protective cloth for medical applications.