The immune system of mammals includes a complex array of cells and molecules, which interact to provide protection from pathogenic microorganisms. The beneficial role played by lactic acid bacteria and milk-derived peptide in the humans, including the effects on the immune system, has been extensively reported. They are present in dairy products and are frequently used as nutraceuticals to some improve some biological functions in the host. The activation of the systemic and secretory immune response by lactic acid bacteria and milk-derived peptide requires many complex interactions among th different constituents of the intestinal ecosystem. The aim of this review was to make the point about the immunological potential of lactic acid bacteria and milk-derived peptide.