Biomimetic smart nanochannels have been studied extensively to achieve the precise ionic transport compared to biological ion channels. Similar to ion channels in living organisms, biomimetic smart nanochannels can respond to various stimuli, which allows for promising applications in many fields. In this review, we mainly summarize the recent advances in the design of biomimetic stimuli-responsive nanochannels and their potential applications including biosensors and drug delivery. Finally, an outlook on the challenges and opportunities for biomimetic stimuli-responsive nanochannels is provided.