As emerging alternatives to natural enzymes, nanoscale materials featuring enzyme‐like catalytic behaviors (nanozymes) exhibit some attractive merits including robust activity, low cost, and easy‐to‐regulate performance. These merits have enabled them to be intensively used in the biomedical field in recent years. To remedy the lack of catalytic selectivity in most nanozymes, deoxyribonucleic acid (DNA) chains with specific recognition functions are utilized to integrate with nanozymes to produce various nanozyme–DNA combinations via adsorption/desorption. In the formed combinations, the DNA component provides the molecular/ionic recognition role, and the nanozyme part offers response with catalytically amplified signals, enabling them to detect analytes and biomarkers selectively and sensitively. To highlight this interesting topic, here we made a critical review of the interactions between nanozymes and DNA and their applications in biosensing and disease diagnosis. First, strategies for the conjugation of DNA chains onto nanozyme surface were introduced briefly. Then, the interactions between DNA and nanozymes were summarized in detail, where flexible modulations of nanozyme activity by DNA adsorption/desorption as well as various factors were analyzed, and potential impacts caused by nanozymes on the recognition characteristics of DNA chains were pointed out. After that, typical applications of DNA‐mediated nanozyme modulation in toxic ion sensing, health risk factor monitoring, and biomedical diagnosis were introduced. In the end, prospects of the combination of nanozymes and DNA chains were presented, and future challenges of the emerging field were also discussed, to attract more interest and effort to advance this promising area.