Environmental cues have been proven as a pivotal participant in the shaping of immune system via metabolic control, epigenetic reprogramming and direct interaction on some key signaling pathways. Regulatory T cells (Tregs), the major negative component among immune cells, are also a considerably dynamic, plastic and heterogenous cell population. As such, Tregs are sensitive to environmental factors, which can determine the induction of their subsets such as tissue-specific Tregs, diet-induced Tregs and microbiota-induced Tregs. Recently, short-chain fatty acids (SCFA), mainly produced by the gut microbiota, gained much attention regarding its interrelationship with the immune system. Butyrate has been shown to be a powerful and versatile SOFA, part of its beneficial effect is exerted through the induction of different types of peripheral Tregs. Here, we provide a brief overreview for the role of butyrate in the induction of peripheral Tregs in disease conditions.