Both developed and developing countries are witnessing a critical increase in chronic inflammatory diseases that target different organs and especially affect productive age people. Therefore, it is implicit that environmental factors – modes of delivery and breastfeeding, nutrition, pollution, food additives, medicines, and smoking, to name just a few – play an important role in the origin and persistence of organ damage. The main way by which these factors carry out their actions is represented by intestinal microbiota, which constitutes a complex and changing living ecosystem located in the digestive tract and which performs basic functions of homeostasis not only for the intestine but also for the entire human organism. Parallel to this phenomenon, in the last few years, researchers have become aware of the extra-skeletal effects of vitamin D, above all regarding the maintenance of immunological tolerance and strengthening of the intestinal barrier. In addition, a large portion of circulating vitamin D comes through diet and must therefore be absorbed at the intestinal level. The hypothesis of an interaction between vitamin D and intestinal microbiota, therefore, seems plausible, especially in cases of qualitative or quantitative alterations of the latter. Likewise, the possible effects of vitamin D supplementation on the composition of the microbiota itself must be taken into consideration. These are the topics discussed in this article.