Fat body metabolism plays crucial roles in each aspect of insect life traits. Although neuropeptides have been documented to be one of the major neuroendocrinal regulators involved in fat body metabolism, the detailed regulatory mechanism is poorly explored. Here, we conducted comparative metabolome and transcriptome analyses of fat body between wide type (WT) and adipokinetic hormone/corazonin-related peptide (ACP) loss of function mutants of the migratory locust, Locusta migratoria. We found that knockout of ACP resulted in significantly reduced fat body triacylglycerol content but enhanced abundance of phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine. Additionally, the expression levels of genes involved in triacylglycerol and phospholipid synthesis and degradation were significantly altered in the fat body of ACP mutants. Moreover, female ACP mutants displayed much higher fecundity compared to WT females. These findings highlight the important role of neuropeptide ACP in fat body lipid metabolism homeostasis in locusts.