Stimuli-responsive hydrogels have attracted considerable attention for use as smart materials, such as in molecular sensors and drug delivery systems. With a focus on their crosslinking density, we have prepared various molecule-responsive hydrogels that undergo volume changes in response to target molecules based on the association/dissociation of molecular complexes that act as crosslinkers. Recent developments in polymerization techniques enabled us to design various types of polymer nanomaterials. This focus review provides a short overview of our recent studies on the nano-and micro-structured molecule-responsive hydrogels prepared using various polymerization techniques, such as photopolymerization, surface-initiated atom transfer radical polymerization, and soap-free emulsion polymerization. The nano-and micro-structured molecule-responsive hydrogels showed not only rapid swelling/shrinkage in response to a target molecule owing to their large surface area but also smart functions, such as autonomous molecule-responsive microchannel flow regulation and highly sensitive detection of a target molecule. The smart functions of nano-and micro-structured molecule-responsive hydrogels can provide tools for constructing, for example, sensors, microdevices and smart biomaterials.