Erianin, a bioactive compound extracted from Dendrobium, a traditional Chinese medicine, exhibits remarkable anti-cancer properties through diverse molecular mechanisms and has attracted the attention of medicinal chemists. However, the low solubility in water, rapid metabolism and elimination from the body lead to poor bioavailability of Erianin, and greatly hinder its clinical application. The development of new Erianin derivatives is continuously proceed to improve its anticancer effects. In recent years, although important progress in the development of Erianin and the publication of some reviews in this aspect, the mechanism against various cancers, pharmacokinetic study, structural modification as well as structure-activity relationships have not been thoroughly considered. This review is aimed at providing complete picture regarding the above aspects by reviewing studies from 2000 to 2023.06. This review also supplies some important viewpoints on the design and future directions for the development of Erianin derivatives as possible clinically effective anticancer agents.