Mycotoxins are toxic secondary metabolites generated from toxigenic fungi in the contaminated food and agro-food, which have been regarded as a serious threat to the food safety and human health. Therefore, the control of mycotoxins and toxigenic fungi contamination is of great significance and has attracted the increasing attention of researchers. As we know, nano-semiconductors have many unique properties such as large surface area, structural stability, good biocompatibility, excellent photoelectrical properties, and low cost, which have been developed and applied in many research fields. Recently, nano-semiconductors have also been promisingly applied in mitigating or controlling mycotoxins and toxigenic fungi contaminations in food and agro-food. In this review, the type, occurrence, and toxicity of main mycotoxins in food and agro-food were introduced. Then, a variety of strategies to mitigate the mycotoxin contamination based on nano-semiconductors involving mycotoxins detection, inhibition of toxigenic fungi, and mycotoxins degradation were summarized. Finally, the outlook, opportunities, and challenges have prospected in the future for the mitigation of mycotoxins and toxigenic fungi based on nano-semiconductors.