Food safety issues are a worldwide concern. Pathogens, toxins, pesticides, veterinary drugs, heavy metals, and illegal additives are frequently reported to contaminate food and pose a serious threat to human health. Conventional detection methods have difficulties fulfilling the requirements for food development in a modern society. Therefore, novel rapid detection methods are urgently needed for on-site and rapid screening of massive food samples. Due to the extraordinary properties of nanozymes and aptamers, biosensors composed of both of them provide considerable advantages in analytical performances, including sensitivity, specificity, repeatability, and accuracy. They are considered a promising complementary detection method on top of conventional ones for the rapid and accurate detection of food contaminants. In recent years, we have witnessed a flourishing of analytical strategies based on aptamers and nanozymes for the detection of food contaminants, especially novel detection models based on the regulation by single-stranded DNA (ssDNA) of nanozyme activity. However, the applications of nanozyme-based aptasensors in food safety are seldom reviewed. Thus, this paper aims to provide a comprehensive review on nanozyme-based aptasensors in food safety, which are arranged according to the different interaction modes of ssDNA and nanozymes: aptasensors based on nanozyme activity either inhibited or enhanced by ssDNA, nanozymes as signal tags, and other methods. Before introducing the nanozyme-based aptasensors, the regulation by ssDNA of nanozyme activity via diverse factors is discussed systematically for precisely tailoring nanozyme activity in biosensors. Furthermore, current challenges are emphasized, and future perspectives are discussed.