Silk fibroin can be used to extend the shelf life of many different foods. Using cell-based assays, silk fibroin is shown to be neither mutagenic nor genotoxic. A 28-day repeated dose study yielded no negative clinical sign observations. Analyses of pepsin digestion and bioinformatics revealed no allergenic concerns. Silk fibroin has been found to be safe for human consumption. Recent research has shown that silk fibroin protein (SF) can extend food shelf life by mitigating spoilage markers such as oxidation and dehydration. Because of the possibility of this protein becoming more widely used, its safety was thoroughly investigated. First, five bacterial strains were subjected to a bacterial reverse mutation test (Ames test). Silk fibroin's unique properties have prompted extensive research into its applicability and use in the medical, cosmetic, and food industries. The ability of silk fibroin to extend the shelf-life of various classes of foods by minimising oxidation and dehydration, the potential of this protein to reduce food waste, and the corresponding likelihood of widespread consumption of silk fibroin in the context of extending the shelf-life of foods necessitates an assessment of the potential risks. Food waste has far-reaching socioeconomic and environmental consequences for countries of all income levels, including food security, nutrition, and economic development. The United Nations Food and Agriculture Organization (FAO) estimates that more than one-third of all food produced globally each year are wasted, primarily due to spoilage prior to consumption. Fresh foods are especially vulnerable to waste caused by cold chain breaks, with an estimated 50% of produce and 30% of proteins wasted before reaching the end-consumer. Furthermore, the decomposition of wasted food, as well as the energy and water inputs required for redundant production, processing, and distribution, are extremely harmful to the environment. Despite moderate improvements in the food packaging industry over the last several decades, the cold chain and single-use plastics remain the industry standard. Naturally-occurring silk proteins, primarily silk fibroin protein, demonstrated the ability to form an invisible barrier on the surface of food that reduces oxidation and moisture loss, both of which are key hallmarks of spoilage. Silk fibroin, as a highly tunable biomaterial with unique mechanical properties, offers a promising solution for extending the shelf-life of a wide range of food items. This study aims to build on the historical consumption of silk fibroin-containing foods (e.g. silkworms and their derivatives) in regions such as the Americas and East and Southeast Asia in order to assess the safety of silk fibroin using both in vitro and in vivo methods.