Gangliosides are acid glycosphingolipids widely distributed in most vertebrate tissues and fluids. They are present in mammalian milk, where they are almost exclusively associated with the membrane fraction of the fat globule. In human milk, the content and individual distribution of gangliosides changes during lactation, GD3 being the most abundant ganglioside in colostrum, while in mature milk, GM3 is the major individual species. Gangliosides function as “unintended” target receptors for bacterial adhesion in specific tissues. After oral administration, they can be putative decoys that interfere with pathogenic binding in the intestine, this being the main mechanism by which these compounds can prevent infection. Ganglioside-supplemented infant formula has been reported to modify the intestinal ecology of preterm newborns, increasing the Bifidobacteria content and lowering that of Escherichia coli. In addition, the influence of dietary gangliosides on several parameters related to the development of intestinal immune system, such as cytokine and intestinal IgA production, has also been described in animal models. Recently, the influence of GM3 and GD3 on dendritic cell maturation and effector functionalities has also been reported, suggesting a role for these milk gangliosides, especially GD3, in modulating the process of oral tolerance during first stages of life. In summary, dietary gangliosides may have an important role in the modification of intestinal microflora and the promotion of intestinal immunity development in the neonate, and consequently in the prevention of infections during early infancy.