Mucosa-associated lymphoid tissue (MALT) is a solitary organized mucosa-associated lymphoid follicles and is characterized as lacking afferent lymphatics, therefore only taking up exogenous antigens through its follicle-associated epithelium. The gastrointestinal mucosa maintains a tolerogenic microenvironment to protect the body from unwanted induction of the immune response to continuously exposed commensal microorganisms and food antigens. Considering that 90% of infections occur in mucosal areas, it is conceivable that using mucosal vaccination to establish protective immunity in this frontline of pathogen infection offers great advantages. However, currently available oral vaccines are limited compared to parenteral vaccines. This limited availability is related with the lack of an effective antigen delivery system and a strong adjuvant to stimulate immunity. Among mucosal cells, M cells are specialized epithelial cells that take up exogenous antigens and are mainly localized in isolated lymphoid follicles in the small intestine and in follicle-associated epithelium of Peyer’s patches. Characteristics such as high transcytotic activity and intracellular pockets containing various antigen-presenting cells make M cells important effectors in antigen delivery and initiators of antigen-specific mucosal immunity. These features of M cells make them attractive targets in oral mucosal vaccine delivery. We have concentrated our efforts to elaborate efficient antigen delivery system to M cells to develop the effective oral mucosal vaccines. Initially, peptide ligands capable of targeting conjugated antigen into M cells were selected from phage display library panning against in vitro human M-like cells. Recently, we identified the antigen-targeting ability and mucosal immune-modulating activity of human cathelicidin anti-microbial peptide LL-37. Finally, adjuvant activity of the ligands and peptide in mucosal immunization was confirmed by using antigens from pathogenic viruses. (This work was supported by a grant from the Next-Generation BioGreen 21 Program (Project No. PJ011801), Rural Development Administration, Republic of Korea.)