Porcine epidemic diarrhea virus (PEDV) causes severe intestinal damage, posing significant threats to the swine industry. Fucoidan (FUC), a biologically active compound, exhibits antiviral activity against multiple viruses. This study aimed to investigate the protective effects of FUC on PEDV-induced intestinal injury in piglets and explore its underlying mechanisms. A total of 28 healthy crossbred piglets were randomly allocated into four experimental groups using a 2 × 2 factorial design: (1) a control group, (2) an FUC group, (3) a PEDV group, and (4) an FUC+PEDV group. From day 4 to day 10, the piglets in the FUC and FUC+PEDV groups were orally administered fucoidan at a dosage of 20 mg/kg body weight (BW) each day. On day 8, the piglets in the PEDV and FUC+PEDV groups were orally administered PEDV at a dose of 3 × 10^5.5 TCID₅₀. The results show that FUC supplementation significantly decreased plasma DAO activity (p < 0.05) and increased the villus height, villus area, as well as the villus height/crypt depth (p < 0.05) in the intestine when compared to the PEDV-infected piglets. This indicates that FUC could alleviate the disruption of intestinal morphology and function caused by PEDV infection. FUC enhanced the antioxidant capacity of the piglets by increasing SOD and GSH-Px activity. Transcriptional profiling combined with quantitative analysis revealed that FUC regulates immune responses, substance transport, and arginine metabolism. Notably, FUC downregulated arginase 1 expression, which may redirect arginine toward nitric oxide synthesis, thereby establishing an antiviral state in the host. These findings highlight the potential application of FUC as a natural agent for mitigating PEDV-induced intestinal damage and improving gut health. Additionally, monitoring the health status of piglets is necessary when FUC is applied in practical applications.