Cotton is an important crop, and terpenoids form the largest group of natural products. Gossypol and related sesquiterpene aldehydes in cotton function as phytoalexins against pathogens and pests but pose human health concerns, as cotton oil is still widely used as vegetable oil. We report the isolation and identification of four enzymes and the recharacterization of one previously reported P450. We are now close to the completion of the gossypol pathway, an important progress in agricultural and plant sciences, and the data are beneficial to improving food safety. Among the six compounds (intermediates) isolated following gene silencing, one affected plant disease resistance significantly. Thus, these “hidden natural products” harbor interesting biological activities worthy of exploration.