Porcine epidemic diarrhea (PED), a highly contagious and lethal enteric disease in piglets, is characterized by diarrhea, vomiting, and dehydration, with high mortality in neonatal piglets. Despite the nationwide use of attenuated and inactivated vaccines, the outbreak of PED is still a major problem in the swine industry. Virus-like particles (VLPs) are artificial nanoparticles similar to viruses that are devoid of genetic material and are unable to replicate. VLPs have good safety profiles and elicit robust cellular and humoral immune responses. Here, we generated PED VLPs in eukaryotic cells and examined their immune responses in mice. We found that the M protein is essential for the formation of PED VLPs. Interestingly, PED VLP formation was decreased in the presence of E proteins and increased in the presence of N proteins. Both IgG and IgA antibodies were induced in mice immunized with PED VLPs. Moreover, these antibodies protected against PED virus infection in Vero cells. PED VLPs immunization induced Th2-dominant immune responses in mice. Our results indicate that PED VLPs induce strong immune responses in mice, suggesting that the VLP-based vaccine is a promising vaccine candidate.