This study investigated the therapeutic efficacy and underlying mechanisms of seawater pearl hydrolysate (SPH) against PMS in an ovariectomized (OVX) rat model, focusing on the estrogen receptorα (Erα)/mitogen-activated protein kinase (MAPK)/cAMP-responsive element-binding protein (CREB) signaling pathway.<h4>Methods</h4>A PMS rat model was established via bilateral ovariectomy. This evidence concerns the gene CREB1 and premenstrual tension.