Early-life experiences profoundly influence neurocognitive development, significantly shaping a child’s academic performance, behavior, and overall quality of life. Environmental factors, including exposure to neurotoxicants such as manganese, can devastate the nervous system, with the developing nervous system being especially more susceptible to neurotoxicity. Walnuts are interesting in that they contain potent bioactive micro- and macronutrients, such as ω-3 fatty acids, flavonoids, melatonin, vitamin E, selenium, and ɣ-tocopherol, all of which play an essential role in brain health. Previously, we showed the potential of a maternal diet enriched with African walnuts to modulate gene expression differentially and enhance cortico-hippocampal histomorphology in rat offspring. This present study investigated a maternal walnut-enriched diet (WED) as a potentially protective factor against MnCl2-induced developmental neurotoxicity in rats during gestation and pre-weaning. The offspring of rats treated with MnCl2 (100 mg/kg) showed a reduction in working memory and emotional stability, but these effects were restored by WED. The aberrations in histomorphology of the PFC and hippocampus due to Mn were also abated by WED, and gene expression dysregulation was prevented. Similarly, inflammatory cytokine levels and perturbations in the cholinergic system were significantly reduced by walnut supplementation. These findings suggest that WED may help prevent deficits in behavior, structural alterations, and functional dysregulation resulting from manganese neurotoxicity in developing rats. This study highlights the potential of dietary interventions to protect against neurotoxicity and promote healthy brain development. Further research is needed to determine the potential implications of these findings for clinical practice and public policy.