A simple and versatile approach is proposed to use cross-linked polypeptide hydrogels as templates for silica mineralization, allowing the synthesis of polypeptide-silica hybrid hydrogels and mesoporous silica (meso-SiO(2)) by subsequent calcination. The experimental data revealed that the cross-linked polypeptide hydrogels comprised of interconnected, membranous network served as templates for the high-fidelity transcription of silica replicas spanning from nanoscale to microscale, resulting in hybrid network comprised of interpenetrated polypeptide nanodomains and silica. The mechanical properties of these as-prepared polypeptide-silica hybrid hydrogels were found to vary with polypeptide chain length and composition. The synergy between cross-link, hydrophobic interaction, and silica deposition can lead to the enhancement of their mechanical properties. The polypeptide-silica hybrid hydrogel with polypeptide and silica content as low as 1.1 wt% can achieve 114 kN/m(2) of compressive strength. By removing the polypeptide nanodomains, mesoporous silicas with average pore sizes ranged between 2 nm and 6 nm can be obtained, depending on polypeptide chain length and composition. The polypeptide-silica hybrid hydrogels demonstrated good cell compatibility and can support cell attachment/proliferation. With the versatility of polymer chemistry and feasibility of amine-catalyzed sol-gel chemistry, the present method is facile for the synthesis of green nanocomposites and biomaterials.