Metabolism is fundamental to survive and perpetuation of the species. Organisms regulate metabolism through behavior and a series of physiological change. Negative energy balance (e.g. anorexia nervosa) or excessive energy deposits (e.g. obesity, diabetes) mainly caused by imbalance between energy intake and energy consumption. And, in severe cases, metabolic disorders impair growth and reproductive function. The central nervous system, especially the hypothalamus, is vital for regulating energy metabolism and balance. Hypothalamus Kisspeptin (encoded by the Kiss1 gene) have well-established roles in regulating reproductive axis and function. Recent evidence suggests that Kisspeptin signaling is critical for metabolism and energy balance. AVPV/PeN Kiss1 neurons send inhibitory GABAergic projections to the PVH and dorsomedial hypothalamic nucleus (DMH) as described. While, Arc Kiss1 neurons can release excitatory transmitter glutamate to PVH and DMH. And, Arc Kisspeptin directly excites POMC/CART neurons through mGluRs group I. In addition, Arc Kiss1 neurons inhibit Arc NPY/AgRP neurons through mGluRs group II/III or release inhibitory transmitters to Arc NPY/AgRP neurons by an indirect way. Besides, energy imbalance can stimulate the release of leptin and adiponectin from adipose tissue, insulin from pancreas and ghrelin from gastrointestinal tract. These peripheral metabolic factors can directly or indirectly stimulate Kiss1 neurons in hypothalamus. This review focuses on the metabolism function of Kisspeptin neurons in the energy input and energy expenditure, which provides important implications of Kisspeptin-based therapies for metabolic-related diseases.