Silk-based biomaterials are useful platforms to achieve the design of biomimetic hierarchical microstructures and the co-loading of various bioactive ingredients. Silk fibroin nerve conduits provide suitable microenvironment to accelerate functional recovery of peripheral nerves. Different optimizing strategies are available for silk fibroin biomaterials to favor the nerve regeneration, which would satisfy the needs of various nerve tissue repair. Bioactive silk conduits have promising future in large-size peripheral nerve regeneration.