The gut is a fundamental organ in controlling human health. Recently, researches showed that substances in the intestine can alter the course of many diseases through the intestinal epithelium, especially intestinal flora and exogenously ingested plant vesicles that can be transported over long distances to various organs. This article reviews the current knowledge on extracellular vesicles in modulating gut homeostasis, inflammatory response and numerous metabolic disease that share obesity as a co-morbidity. These complex systemic diseases that are difficult to cure, but can be managed by some bacterial and plant vesicles. Vesicles, due to their digestive stability and modifiable properties, have emerged as novel and targeted drug delivery vehicles for effective treatment of metabolic diseases.