The morphological structure reconstruction and functional recovery of long-distance peripheral nerve injury (PNI) are global medical challenges. Biodegradable nerve scaffolds that provide mechanical support for the growth and extension of neurites are a desired way to repair long-distance PNI. However, the synchrony of scaffold degradation and nerve regeneration is still challenging. Here, a novel bioinspired multichannel nerve guide conduit (MNGC) with topographical cues based on silk fibroin and ε-polylysine modification was constructed. This conduit (SF(A) + PLL MNGC) exhibited sufficient mechanical strength, excellent degradability, and favorable promotion of cell growth. Peripheral nerve repairing was evaluated by an in vivo 10 mm rat sciatic model. In vivo evidence demonstrated that SF(A) + PLL MNGC was completely biodegraded in the body within 4 weeks after providing sufficient physical support and guide for neurite extension, and a 10 mm sciatic nerve defect was effectively repaired without scar formation, indicating a high synchronous effect of scaffold biodegradation and nerve regeneration. More importantly, the regenerated nerve of the SF(A) + PLL MNGC group showed comparable morphological reconstruction and functional recovery to that of autologous nerve transplantation. This work proved that the designed SF(A) + PLL MNGC has potential for application in long-distance PNI repair in the clinic.