Three new sesquiterpene dimers, commiphoratones C–E (1–3), unprecedented carbon skeletons possessing a spiro center, were isolated from Resina commiphora. Their structures were assigned by spectroscopic methods, NMR chemical shifts and ECD calculations, and X-ray diffraction analysis. The framework of 1–3 represents a rare ring system of 10/6/5/3 between highly oxidized germacrane sesquiterpene and bicyclic sesquiterpene containing a bicyclo[3.1.0]hexane core via a [2 + 4] cycloaddition reaction. A plausible biosynthetic pathway for 1–3 is also proposed. Biological studies showed that they reduce cellular lipid accumulation in metabolism of fatty acids by regulating the AMPK/ACC pathway in hepatocytes.