Agricultural products are perishable and easily contaminated by spoilage microorganisms or foodborne pathogens, causing decay of food and illness in consumers. Chlorine dioxide (ClO 2) has many advantages as a fungicide in comparison to chlorine, NaClO, and ozone, and it can be used for sterilization and preservation due to its strong oxidizing properties. ClO 2 gas is more widely used in food safety and food preservation than its aqueous solutions. However, the ClO 2 gas produced on a large scale from a chemical reactor cannot be applied to food in small packages. Several recent reports have discussed the use of ClO 2 self-releasing packaging. This article highlights the systematic evaluation of the performance of ClO 2 alone and in combination with other treatments, such as 1-MCP, chitosan, and UV irradiation, in maintaining food safety and freshness of agricultural products. This article also focuses on the biological functions and mechanisms of ClO 2-mediated preservation of plant or animal food, including damage to the cell wall and the membrane of pathogens, inhibition of ethylene biosynthesis, restoration of redox balance, and change of the compound structure of toxins, such as pesticides, insecticides, and mycotoxins.