During the last decade, probiotics have been established to be important mediators of host immunity. Their effects on both innate and adaptive immunity have been documented in the literature. Although several reports have correlated different strains of bacteria as probiotics, their effects on immunity vary. Clearly, there is a complex interplay between various constituents of probiotics and the immune response in humans. The role of probiotics on natural killer (NK) cells in the gut has been the subject of a few reports. In this review, we summarize the reported findings on the role of probiotics in the activation of gut-associated NK cells and the response of NK cells to stimuli elicited by probiotics and their microenvironment. The effects of probiotics on the activation of NK cells and their secretion of immune factors (eg, interferon− γ, tumor necrosis factor− α, interleukin-2, etc.) are discussed in regard to their clinical significance in various diseases. Current investigations are being pursued, in particular, on the role of probiotics-activated NK cells in promoting the adaptive immune response against pathogens.