Ent-labdane diterpenoid lactones, the principal constituents of Andrographis paniculata, have a wide range of pharmacological effects, such as antibacterial, anti-viral, anti-inflammatory, antipyretic, and anti-cancer effect, etc. In this review the biotransformations of four principal ent-labdane diterpenoid lactones of A. paniculata are discussed from the following aspects: substrates and types of reaction, transformation systems, and structure activity relationships. Moreover, the currently-existing problems and the prospects are also described to provide reference for further studying the biotransformation of ent-labdane diterpenoid lactones of A. paniculata.