Peripheral nerve injury is a worldwide challenge in the clinic. Although autologous nerve is considered the gold standard for bridging large nerve defects (> 5 mm), donor-site morbidity, limited sources of donor nerves and other potential side effects restrict its application in nerve regeneration. Nerve guidance conduits have become increasingly popular as a promising alternative to autologous nerve repair and regeneration. The evolution of nerve guidance conduits from nondegradable materials to various biodegradable materials subsequently results in enhanced properties, such as superior biodegradability, a mimetic extracellular matrix and an optimal structure. This review describes current therapies for nerve repair and the mechanism and evolution of nerve guidance conduits with advantages and limitations; proposes the detailed requirements of ideal nerve guidance conduits; and emphasizes the applications of natural polymers, including collagen, chitosan, alginate, gelatin, silk fibroin and hyaluronic acid, in nerve regeneration with the incorporation of various functional materials, chemical modifications and feasible techniques to promote cell proliferation and axon regeneration. Compared with natural polymers, advanced nerve guidance conduits have considerable potential for nerve regeneration in the clinic.