Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by transgenerationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for gestation-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish an exposure threshold due to nutrient deficiencies or other environmental factors that can result in clinically relevant epigenetic alterations that modulate disease risks in the fetus. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development. This review unravels the potential roles of the functional epigenome for targeted intervention to ensure optimal fetal brain development and its performance in later life.