The contamination of heavy metals (e.g., Hg, Pb, Cd and As) poses great risks to the environment and human health. Rapid and simple detection of heavy metals of considerable toxicity in low concentration levels is an important task in biological and environmental analysis. Among the many convenient detection methods for heavy metals, DNA-inspired gold nanoparticles (DNA-AuNPs) have become a well-established approach, in which assembly/disassembly of AuNPs is used for colorimetric signaling of the recognition event between DNA and target heavy metals at the AuNP interface. This review focuses on the recent efforts of employing DNA to manipulate the interfacial properties of AuNPs, as well as the major advances in the colorimetric detection of heavy metals. Beginning with the introduction of the fundamental aspects of DNA and AuNPs, three main strategies of constructing DNA-AuNPs with DNA binding-responsive interface are discussed, namely, crosslinking, electrostatic interaction and base pair stacking. Then, recent achievements in colorimetric biosensing of heavy metals based on manipulation of the interface of DNA-AuNPs are surveyed and compared. Finally, perspectives on challenges and opportunities for future research in this field are provided.