Tryptanthrin and its derivatives, representing a type of alkaloids with indoloquinazoline structures, were first obtained from blue plants and indigo, and then extracted from fungi, marine bacteria and a number of many other natural sources. Various strategies for their chemical synthesis have been reported while tryptanthrin biosynthesis has been less investigated. Tryptanthrin and its derivative products have a broad range of pharmacological and biological functions. In this review, we cover the sources, chemical synthesis and biosynthesis, modes of action and biological activities of tryptanthrin and its derivatives.