With soft micro- and nanopatterned materials becoming increasingly useful for various optical, mechanical, electronic, microfluidic, and optofluidic devices, the extension of this paradigm to a pure protein-based material substrate provides entirely new options for such devices. Silk fibroin combines the properties of an ideal nanoimprint resist with superior optical quality and biocompatibility, making it a new technology platform that seamlessly combines nanophotonics, bio-polymeric, and biocompatible materials.