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Periodical fluctuation is a common phenomenon in food safety supervision. The existing literature on China’s food safety supervision mainly analyzes periodical fluctuation by statistical methods. This paper provides a theoretical explanation by building an evolutionary game model between food enterprises and supervision institutions under bounded rationality. The “Sanlu milk powder” food safety incident is taken as a typical example to conduct numerical simulations of the food safety supervision game. Moreover, the determining factors in the periodical fluctuation in food safety supervision are analyzed in detail by numerical simulations, including the initial states and benefit–cost parameters. The results show that the periodical fluctuation and probability of supervision failure are influenced by the initial states. Supervision institutions should discard historical path dependence and adjust their supervision-intensity timing according to its actual effects. In addition, blindly increasing rewards or punishments cannot effectively restrain the fluctuation or reduce food safety incidents. To reduce the occurrence of food safety incidents and decrease periodical fluctuation, supervision institutions should reduce supervision costs by using information technology, establish strict food safety standards to eliminate “small-workshop” enterprises, be more aware of risks and appropriately overestimate the added benefits for food enterprises of becoming involved in illegal production.