The eyestalk ganglion is a predominant neuroendocrine organ in crustaceans that synthesize crustacean hyperglycemic hormone (CHH) family participating in physiological activities such as ovarian development, glucose homeostasis, and molting. Red pigment concentrating hormone (RPCH) contributes to a diversity of physiological influences, including ovarian development; however, its role in modulating CHH-family neuropeptides in the eyestalk ganglion remains unclear. In this study, we characterized the putative RPCH receptor (RPCHR) in the mud crab Scylla paramamosain and revealed that it was expressed in a variety of tissues, including the eyestalk ganglion. In vivo administration of mature RPCH peptide significantly restrained vitellogenesis inhibiting hormone (VIH) expression and significantly enhanced RPCHR, crustacean hyperglycemic hormone (CHH) and molt inhibiting hormone (MIH) gene expression, while in contrast, in vivo injection of RPCH-dsRNA for knockdown dramatically enhanced VIH expression and decreased RPCHR, CHH and MIH expression in the eyestalk ganglion. The present study comprehensively reports that RPCH may be responsible for the regulation of ovarian maturation, glucose homeostasis, and molting in S. paramamosain through the modulation of CHH family neuropeptides in the eyestalk ganglion.