Drought events have become more severe under climate change, and this can pose a major threat to the survival of various organisms.  The molecular mechanisms involved in dehydration resistance are not well known.  Here, adults of the migratory locust, Locusta migratoria, were subjected to food-mediated dehydration, and adipokinetic hormone (AKH) signaling was found to play a key role in regulating dehydration resistance.  Specifically, dehydration shortened the lifespan, increased the body weight loss, and reduced the water loss rate in adult locusts.  Global transcriptome profiles revealed variations in tissue-specific gene expression between dehydration-resistant locusts and normal locusts.  Importantly, dehydration selection and exposure induced prominent expression of AKH genes in the retrocerebral complex of adult locusts.  Furthermore, individual knockdown of AKH1, AKH2, or AKH receptor (AKHR) accelerated water loss and shortened the lifespan of adult locusts under dehydration conditions, and trehalose supplementation ameliorated the negative effects caused by interference with AKH or AKHR.  These findings demonstrated that AKH/AKHR signaling-dependent trehalose metabolism plays a crucial role in regulating locust dehydration resistance and thus provide novel insights into the regulatory mechanism underlying drought resistance.