ABSTRACT DNA nanostructures have emerged as a highly programmable platform with applications spanning nanomedicine, biosensing, and molecular machinery. Although their design is primarily governed by sequence‐encoded base pairing, growing evidence indicates that the chemical environment critically modulates their assembly, stability, and function. This review systematically summarizes how key environmental factors, including pH, cation identity, and additives, influence DNA nanostructures across multiple hierarchical levels. We begin by outlining the fundamental principles of DNA assembly, with emphasis on sequence design, sticky end interactions, and DNA concentration. We then discuss the effects of pH, cation identity, and additives on structural stability and dynamic behavior. Building on these insights, we further explore how environmental responsiveness is harnessed to construct advanced systems for DNA‐based nanodevices, delivery, biosensing, and environmental monitoring. Finally, current challenges and future perspectives are outlined. This review provides a comprehensive framework for understanding and exploiting chemical environment‐mediated regulation in DNA nanotechnology, paving the way for the rational design of adaptive and functional nanomaterials.
Xie et al. (Mon,) studied this question.