Bacillus subtilis produces many chemically-diverse secondary metabolites of interest to chemists and biologists. Based on this, this review gives a detailed overview of the natural components produced by B. subtilis including cyclic lipopeptides, polypeptides, proteins (enzymes), and non-peptide products. Their structures, bioactive activities and the relevant variants as novel lead structures for drug discovery are also described. The challenging effects of fermentation metabolites, isolation and purification, as well as the overproduction of bioactive compounds from B. subtilis by metabolic engineering, were also highlighted. Systematically exploring biosynthetic routes and the functions of secondary metabolites from B. subtilis may not only be beneficial in improving yields of the products, but also in helping them to be used in food industry and public medical service on a large-scale. (C) 2015 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.