Sialic acid (SA) is widely present at the end of the sugar chain of glycoproteins and glycolipids on the surface of animal and microbial cells and is involved in many physiological activities between microbial and host cells. Notably, these functions are attributed to the diversity of these SA types, their different transformation pathways, and their metabolic actions within the host, which are considered potential targets for affecting various diseases. However, developing disease mitigation strategies is often limited by an unclear understanding of the mechanisms of interaction of the causative agents with their hosts. This review mainly focuses on three types of SA: Neu5Ac, Neu5Gc, and KDN. The sources, main types, and distribution of these SAs are discussed in detail, emphasizing the metabolic processes of different SAs and their interaction mechanisms with the host. This review will help lay a foundation for developing functional foods and SA-targeted intervention strategies.