DNA nanostructures have recently attracted increasing interest in biological and biomedical applications by virtue of their uniquep roperties, such as structuralp rogrammability, multi-functionality,s timuli-responsive behaviors, and excellentb iocompatibility.I np articular,t he intelligent responsivenesso fs mart DNA nanostructures to specific stimuli hasf acilitated their extensive developmenti nt he field of high-performance biosensing and controllable drug delivery.T his minireview begins with different self-assembly strategies for the construction of various DNA nanostructures, followed by the introduction of av ariety of stimuli-responsive functional DNA nanostructures for assembling metastable soft materials and for facilitating amplified biosensing.T he recent achievements of smartD NA nanostructures for controllable drug delivery are highlighted. Finally, the current challenges and possible developments of this promising research are discussed in the fields of intelligent nanomedicine.