The nuclear factor of activated T cells (NFAT) protein induce transcription of cytokine genes required for T-cell activation, including the IL-2 gene. Activation of NFAT normally plays a significant role in inducing immune response. However, excessive activation provokes immunopathological reactions including autoimmunity, transplant rejection and inflammation. Thus, several natural products were screened on the inhibitory activity against the NFAT transcription factor. Among them, Euonymus sieboldiana showed strong inhibitory activity against the NFAT transcription factor without affecting cell viability.