Human milk oligosaccharides (HMOs) are the first prebiotics humans meet in life. HMOs provide many benefits to infants including impact on gut bacteria, promotion of postnatal brain development, and modulation of the immune system. A complex bidirectional communication pathway called the microbiota-gut-brain axis links gut homeostasis and microbial composition with the central nervous system (CNS). Several mechanisms regulated by the gut microbiota are known to affect this axis. Dynamics in microbiota composition changes the metabolite profile in the gut, including neuroactive biomolecules that influence brain function and health. The gut microbiota also has the potential to affect and interact with the neurologic, immunologic and endocrine pathways of the microbiota-gut-brain axis. In this review, we discuss the potential role of HMOs in microbiota-gut-brain axis and CNS disorders, by describing the role of the gut microbiota in relation to brain health and the importance of dietary interventions in manipulating the microbiota-gut-brain axis.