Silk sericin (SS) was used as both a 3-dimensional matrix and reductant for the in situ synthesis of silver nanoparticles (AgNPs) finished on silk fabrics. We demonstrated enhanced UV protection and antibacterial properties using this synthesis which was an environmental friendly approach. Development and optimization was achieved using a central composite design (CCD) in conjunction with the response surface methodology (RSM). The goal was to identify the concentrations of SS and AgNO 3 that produced the optimal balance between UV protection and antibacterial activity, when tested against E. coli and S. aureus. The SS-AgNP bio-nanocomposites were characterized using Scanning Electron Microscope (SEM-EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). Statistical analyses indicated an empirical second-order polynomial could accurately model the experimental values. To confirm that the optimal levels from RSM worked in practice, performance evaluations were conducted, including tests of cytotoxicity, of the durability and stability of UV protection, as well as of the antibacterial activity of the functionalized fabrics after repeated standard washing. The results suggest that these bio-nanocomposites have great potential for multi-functionalization on silk fabrics. Our method has been shown to convert the waste material (SS) to a fabric with high added value.