Sea cucumber is a nutritional aquatic food that is widely consumed in East Asian countries. Employing a rat model of ethanol-induced gastric ulcer, we examined the protective effect of sea cucumber fucoidan (SC-FUC) extracted from Acaudina molpadioides and explored the related mechanisms. Oral administration with 100 mg/kg body weight SC-FUC for 5 days can significantly prevent the formation of gastric ulcer. Moreover, SC-FUC pretreatment could alleviate ethanol-induced histological damage, reverse changes in tissue oxidation and antioxidase activities, and regulate the signalling pathways of mitogen-activated protein kinases and matrix metalloproteinases. This study investigated the ethanol-induced gastric ulcer protective effect of SC-FUC for the first time, and elucidated that the protective mechanisms included anti-oxidation, gastric matrix hydrolysis suppression, and anti-inflammation.