Nature provides a huge range of biological materials, just as ion channels, with various smart functions over millions of years of evolution, and which serve as a big source of bio-inspiration for biomimetic materials. In this critical review, a strategy for the design and synthesis of biomimetic smart nanopores and nanochannels is presented and put into context with recent progress in this rapidly growing field from biological, inorganic, organic to composite nanopore and nanochannel materials, which can respond to single/multiple external stimuli, e.g., pH, temperature, light, and so on. This review is intended to utilize a specific responsive behavior for regulating ionic transport properties inside the single nanopore or nanochannel as an example to demonstrate the feasibility of the design strategy, and provide an overview of this fascinating research field (109 references).