ABSTRACT Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus (LH). The mTOR pathway is an essential component of the Orexin/GPCR downstream signaling network and can be activated and activated by Orexin. This review article summarizes the Orexin system and its inhibition of various diseases through mTOR signaling pathway. In addition, the potential of targeting the Orexin system for treating a wide range of conditions is discussed.