Porcine epidemic diarrhea virus (PEDV) is an enveloped single-stranded RNA virus belonging to the family Coronaviridae. It is the causative agent of porcine epidemic diarrhea, dehydration, vomiting, and high mortality in the piglets. Most of newborn piglets infected by PEDV would be dying and pigs of all ages are also affected with a severe symptoms like massive diarrhea and dehydration.1 Infection with this virus has been become a serious issue in the swine industry and outbreak resulted in serious economic losses in many swine producing countries, notably in Europe and Asia. Recently, new PEDV was noticed and its outbreak affected 23 US states by the end of January of 2014. As secondary substances from natural products are generally low-toxic’s small molecules with high potential for chemical novelty and biological interests, extensive studies on medicinal plants may result in the investigation of new compounds with drug-like properties. It have been reported that about 50,000 species among total 500,000 plants in the world are used in traditional medicine. The recent outbreaks of many virus-related new diseases like severe acute respiratory syndrome (SARS) in 2002-2003, novel influenza H1N1 virus in 2009-2010, continuous other influenza viruses in China, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012-present, and also MERS on May of 2015 in Korea suggest that bioactive compounds from natural products against infectious viruses should be continuously developed for the protection of human health. The main objective of our team using natural plants as research source is finding active compounds against zoonotic diseases by viruses at both human and animal. We have been screened thousands of plant extracts for antiviral activity against PEDV. During this process, Camellia japonica, Saposhnikovia divaricata, and Dryoteris crassirhizoma showed potential inhibitory effects on PEDV replication.4-6 Bioassayguided fractionations of these active extracts afforded many compounds with inhibitory activities against PEDV replication. Herein, the antiviral activities, including action of mechanisms, against PEDV of all isolates were evaluated, and a brief structure-activity relationship was also discussed.