The mammalian immune system comprises a complex array of cells and molecules that interact to provide protection from pathogenic microorganisms. The beneficial role played by lactic acid bacteria and milk-derived peptides in humans, including their effect on the immune system, has been extensively reported. Lactic acid bacteria and milk-derived peptides, which are present in dairy products, are frequently used as nutraceuticals to improve some biological functions in the host. Activation of the systemic and secretory immune response by lactic acid bacteria and milk-derived peptides requires many complex interactions among the various constituents of the intestinal ecosystem. Thus, the aim of this review was to examine in detail the immunological potential of lactic acid bacteria and milk-derived peptides.