Immunoglobulin G (IgG) is the most abundant antibody in human serum and plays a crucial role in systemic and mucosal immunity. Peyer’s patches are specialized lymphoid follicles located in the small intestine, serving as important sites for the initiation of immune responses to gut antigens. Scientific evidence supports the role of IgG in supporting the immune functions associated with Peyer’s patches. IgG antibodies can neutralize pathogens and toxins in the gut, facilitate antigen uptake, and aid in immune exclusion, thereby supporting the mucosal barrier maintained by Peyer’s patches. Several studies have demonstrated that orally administered IgG (e.g., from bovine colostrum or serum) can bind enteric pathogens, prevent their adhesion to the intestinal mucosa, and reduce infection severity, indirectly supporting Peyer’s patch function by lowering antigenic burden and inflammation. Moreover, IgG can modulate immune responses within Peyer’s patches by facilitating antigen presentation and enhancing the development of protective immune memory. While most clinical research focuses on infectious disease prevention and treatment of gut inflammation, the mechanistic link between IgG and the modulation of mucosal immunity via Peyer’s patches is well-established in animal models and supported by translational research. However, direct clinical trials in humans specifically targeting Peyer’s patch function are limited, which is why the evidence is rated as a 4 rather than a 5.