Stimuli-responsive gels have attracted considerable attention as smart materials in the biochemical and biomedical fields, since they can sense environmental changes and induce structural changes by themselves. This paper provides an overview of the important research regarding the design and applications of stimuli-responsive gels that undergo volume changes in response to pH, temperature, electric fields, specific molecules, etc. Especially, the synthetic strategies of molecule-responsive gels that exhibit swelling changes in response to a specific molecule are summarized on the basis of molecular complex and molecular imprinting. This article focuses on two types of molecule-responsive gels, that is, biomolecule-cross-linked gels and biomolecule-imprinted gels as the stimuli-responsive gels that have molecular recognition functions. The stimuli-responsive gels reviewed in this paper are expected to contribute significantly to the development of newer generations of smart biomaterials and self-regulated drug delivery systems.