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Sialic acid (SA) is a kind of functional monosaccharide which exists widely in edible bird’s nest (EBN), milk, meat, mucous membrane surface, etc. SA is an important functional component in promoting brain development, anti-oxidation, anti-inflammation, anti-virus, anti-tumor and immune regulation. The intestinal mucosa covers the microbial community that has a significant impact on health. In the gut, SA can also regulate gut microbiota and metabolites, participating in different biological functions. The structure, source and physiological functions of SA were reviewed in this paper. The biological functions of SA through regulating key signaling pathways and target genes were discussed. In summary, SA can modulate gut microbiota and metabolites, which affect gene expressions and exert its biological activities. It is helpful to provide scientific reference for the further investigation of SA in the functional foods.