Human milk oligosaccharides (HMOs) are the third most important nutrient in human milk and are the gold standard for infant nutrition. Due to the lack of an enzyme system capable of utilizing HMOs in the infant intestine, HMOs cannot be directly utilized. Instead, they function as natural prebiotics, participating in the establishment of the intestinal microbiota as a “bifidus factor.” A crucial colonizer of the early intestine is
Bifidobacterium longum
(
B. longum
), particularly its subspecies
B. longum
subsp.
infantis
, which is the most active consumer of HMOs. However, due to the structural diversity of HMOs and the specificity of
B. longum
strains, studies on their synergy are limited. An in-depth investigation into the mechanisms of HMO utilization by
B. longum
is essential for applying both as synbiotics to promote early intestinal development in infants. This review describes the colonization advantages of
B. longum
in the infant intestinal tract and its metabolic strategies for HMOs. It also summarizes recent studies on the effect and mechanism of
B. longum
and HMOs in infant intestinal development directly or indirectly through the action of metabolites. In conclusion, further structural analysis of HMOs and a deeper understanding of the interactions between
B. longum
and HMOs, as well as clinical trials, are necessary to lay the foundation for future practical applications as synbiotics.