We recently reported the in vitro and in vivo antiobesity effects of Tenebrio molitor larvae, a traditional food in manycountries, but it remains unknown how the larvae affect appetite regulation in mice with diet-induced obesity. We hypothesizedthat the extract of T. molitor larvae mediates appetite by regulating neuropeptide expression. We investigated T. molitorlarvae extract's (TME's) effects on anorexigenesis and endoplasmic reticulum (ER) stress–induced orexigenic neuropeptideexpression in the hypothalami of obese mice. Central administration of TME suppressed feeding by down-regulating theexpression of the orexigenic neuropeptides neuropeptide Y and agouti-related protein. T. molitor larvae extract significantlyreduced the expression of ER stress response genes. These results suggest that TME and its bioactive components arepotential therapeutics for obesity and ER stress–driven disease states.