Proopiomelanocortin (POMC) neurons are major negative regulators of energy balance. A distinct developmental property of POMC neurons is that they can adopt an orexigenic neuropeptide Y (NPY) phenotype. However, the mechanisms underlying the differentiation of <i>Pomc</i> progenitors remain unknown. Here, we show that the loss of the microRNA (miRNA)-processing enzyme <i>Dicer</i> in POMC neurons causes metabolic defects, an age-dependent decline in the number of <i>Pomc</i> mRNA-expressing cells, and an increased proportion of <i>Pomc</i> progenitors acquiring a NPY phenotype. miRNome microarray screening further identified miR-103/107 as candidates that may be involved in the maturation of <i>Pomc</i> progenitors. In vitro inhibition of miR-103/107 causes a reduction in the number of <i>Pomc</i> -expressing cells and increases the proportion of <i>Pomc</i> progenitors differentiating into NPY neurons. Moreover, in utero silencing of miR-103/107 causes perturbations in glucose homeostasis. Together, these data suggest a role for prenatal miR-103/107 in the maturation of <i>Pomc</i> progenitors and glucose homeostasis.