Short-chain fatty acids (SCFAs), especially acetate, propionate and butyrate, are the end products from the intestinal microbial fermentation of dietary fibers and resistant starch. It has been well documented that plasma and colonic SCFAs are associated with metabolic syndromes. Recently, the involvement of SCFAs in energy homeostasis regulation has been extensively studied. The importance of SCFAs on energy metabolism has highlighted the potential of modulating SCFAs as a nutritional target to prevent and counteract metabolism disorders and its associated diseases such as obesity and type 2 diabetes. Here, we summarize the current knowledge about the biological properties of SCFAs with their impact on the energy homeostasis.