Selenium (Se) is an essential trace element for humans and has conveyed great a wide range of interests due to its contribution to health. Presently, the regulatory mechanisms of selenium on human health, especially the regulatory mechanisms of selenium on human intestinal (gut) microflora and its effects on diseases are receiving attention from academic circles. This review involves the effects of selenium on physical health, the relationship between selenium and intestinal microflora, and the progress of research between selenium, intestinal microflora, and diseases. Furthermore, the current status of research on the selenium, intestinal microflora, and diseases is also presented.