Porcine epidemic diarrhea virus (PEDV) is a major enteric coronavirus that causes severe economic losses to the global swine industry. Current vaccines suffer from weak immunogenicity, insufficient mucosal immunity, and a short duration of protection. Nanoparticle delivery systems have emerged as a promising strategy for next-generation vaccine development. In the present study, we constructed an S1-Ferritin nanoparticle vaccine using the SpyTag-SpyCatcher modular conjugation system. The morphology, particle size, and uniformity of the nanoparticle vaccine were systematically characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). After two immunizations, the S-Ferritin nanoparticle vaccine elicited potent humoral and cellular immune responses in both mice and piglets. In piglets, at 2 weeks post booster vaccination, PEDV-specific serum IgG endpoint titers peaked at 1:2560, virus-neutralizing antibody titers reached 1:256 against the JS-2/2015 strain, and serum IFN-γ levels reached 274 pg/mL. All these immunological indicators were significantly higher than those observed in the PEDV-inactivated whole-virus vaccine group. Furthermore, challenge tests showed that the S1-Ferritin nanoparticle vaccine provided complete protection against PEDV infection and significantly reduced the severity of diarrhea and intestinal damage in piglets after challenge. These findings suggest that the S1-Ferritin nanoparticle vaccine constitutes a promising candidate against PEDV infection, though our study is only a preliminary step and subsequent field trials in pigs are still required.