Outbreaks of Crown-of-Thorns Starfish (COTS; Acanthaster planci) are a major cause of destruction of coral communities on the Australian Great Barrier Reef. While factors relating to population explosions and the social interactions of COTS have been well studied, little is known about the neural mechanisms underlying COTS physiology and behaviour. One of the major classes of chemical messengers that regulate physiological and behavioural processes in animals is the neuropeptides. Here, we have analysed COTS genome and transcriptome sequence data to identify neuropeptide precursor proteins in this species. A total of 48 neuropeptide precursors were identified, including homologs of neuropeptides that are evolutionarily conserved throughout the Bilateria, and others that are novel. Proteomic mass spectrometry was employed to confirm the presence of neuropeptides in extracts of radial nerve cords. These transcriptomic and proteomic resources provide a foundation for functional studies that will enable a better understanding of COTS physiology and behaviour, and may facilitate development of novel population biocontrol methods.The Crown-of-Thorns Starfish (COTS) is one of the primary factors leading to coral loss on the Great Barrier Reef, Australia. Our combined gene and proteomic findings of this study reveal the COTS neuropeptidome, including both echinoderm-like neuropeptides and novel putative neuropeptides. This represents the most comprehensive neuropeptidome for an echinoderm, contributing to the evolving knowledge of the COTS molecular neurobiology that may assist towards the development of biocontrol methods.