The plants produce different kinds of bioactive compounds for their primary and secondary growth and metabolism known as metabolites. These metabolites includes flavonoids or polyphenolic compounds, terpenoids and nitrogen containing alkaloids or sulphur compounds having potential to fight against pathogens, to interact with nearby plants and to attract pollinators. They are also important source of human nutrition and health and are used in Indian Ayurveda since ages. Commiphora wightii commonly known as ‘Guggul’ having medicinal values due to the presence of an oleo-gum-resin known as guggulsterone is found in desert regions. Over the time, C. wightii population in their natural habitat have been severely reduced due to the extraction of gum guggulu by local people. The poor seed germination, slow-growing nature, climate change and over-exploitation have brought the plant under critically endangered species recorded by the International Union for Conservation of Nature. The present chapter reviews the biosynthesis of guggulsterone, discovery, prospects and associated challenges with respect to plant tissue culture technology for sustainable production of guggulsterone.