Picrotoxane terpenoids are a unique class of natural products that have the features of a highly crowded polycyclic structure and continuous chiral centres. And it is a group of sesquiterpenes, nor-diterpenes and sesquiterpene alkaloids, which are one of the major active constituents of traditional Chinese medicine. These compounds were usually found in herbs from the Picrodendraceae, Orchidaceae, Menispermaceae, Phyllanthaceae and Coriariaceae families, e.g., Dendrobium nobile, Bccaurea ramiflora, and Coriaria nepalensis. A variety of oxidations and skeletal rearrangements occurring in the basic 6/5 dicyclic skeleton led to various picrotoxane derivatives. Picrotoxane sesquiterpenes are featured with the fused or the bridged γ-lactone and picrotoxane nor-diterpenes in spiro γ-lactone. In some case, they are bearing with highly complex tetra, or pentacyclic structures and up to 12 stereogenic centers. The picrotoxanes not only have been used in the treatment of neurological disorder, cancer and immune system diseases, but also in the indispensable neuropharmacological tool molecules. The diverse structures and biological activities of picrotoxanes have attracted considerable attention. Recently, a number of novel picrotoxanes with significant activities have been reported continuously. Until now, picrotoxane alkaloids and the synthesis of picrotoxane sesquiterpenes had been reviewed. Herein, this review mainly surveyed recently advances in chemical structures and biological activities of picrotoxane terpenoids.