Guggulsterone is a phytosteroid derived from the oleo-gum resin of the critically endangered plant . This molecule has attracted increasing attention due to its excellent biochemistry potential and the compound has consequently been evaluated in clinical trials. With a low concentration in natural resources but wide medicinal and therapeutic value, chemists have developed several synthetic routes for guggulsterone starting from various steroid precursors. Moreover, numerous studies have attempted to modify its structure to improve the biological properties. Nowadays, green and sustainable chemistry has also attracted more attention for advanced chemical processes and reactions in steroid chemistry. The present review aimed to summarize the literature and provide an update about the improvements in the chemical synthesis and structural modification of guggulsterone from the view of green chemistry. Moreover, this review encompasses the improved activities of structurally modified guggulsterone derivatives. We expect that the information provided here will be useful to researchers working in this field and on this molecule.