During childhood and adolescence, the individual is likely to undergo significant internal and external environmental changes and demands. At the same time, this is a time window when neuroplasticity is enhanced, allowing brain structures and circuitries to flexibly adapt or maladapt to the environment. In this context, gut microbiota might be a mediator between the environment and the CNS via multiple pathways that include: (i) the vagus nerve and spinal tract, whose action can be either direct or mediated by the ENS; (ii) the HPA axis; (iii) sex hormones (e.g., estrogens and androgens); (iv) microbes’ production of proinflammatory compounds, which can lead to systemic inflammation and microglia activation; and (v) microbes’ metabolites able to cross the BBB (e.g., SCFAs) and to alter the tryptophan/kynurenine pathways. Gut microbiota can be easily manipulated through diet; thus, it could be a promising therapy target in the redirection of neurodevelopmental trajectories.