The effective uptake of antigens (Ags) by specialized M cells of gut‐associated lymphoid tissues is an important step in inducing an efficient intestinal mucosal immune response. In this study, royal jelly (RJ) was found to stimulate the differentiation of M‐like cells from human Caco‐2 cells in an in vitro M cell model. Furthermore, RJ and protease‐treated royal jelly (pRJ) efficiently enhanced transcytosis of FluoSpheres® carboxylate‐modified microspheres from the apical side to the basolateral side in the model. Therefore, we evaluated the ability of pRJ to induce efficient mucosal immune responses in an in vivo nonhuman primate. Continuous oral administration of commercially available pRJ resulted in a significant enhacement of the antigen‐specific IgA response in stool sample. Interestingly, Caco‐2 monolayer assay demonstrated that ether extracts from pRJ efficiently increased the expression level of a universal M cell marker, glycoprotein 2 (gp2). These findings suggest that pRJ exhibits mucosal immunomodulatory properties via stimulation of effective uptake of Ags through M cells.