Chemical study on the mangrove Bruguiera gymnorrhiza collected from Zhanjiang has resulted in the isolation of an unusual novel macrocyclic polydisulfide, neogymnorrhizol (1), which possesses an un-precedented carbon skeleton characterized by a twenty-membered macrocycle that is composed of four repeated 1,3-dimercaptopropan-2-ol units, along with four known related compounds. The structure of the new compound 1 was determined by detailed spectroscopic data analysis (IR, ¹H NMR, ¹³C NMR, 2D NMR, MS, etc.). The known compounds, namely gymnorrhizol (2a), bruguiesulfurol (3), brugierol (4) and isobrugierol (5), were determined by either an X-ray diffraction analysis or comparison with the data reported in the literatures. A plausible biogenetic origin of these uncommon polydisulfides and their biogenetic relationship were also discussed. In bioassay, compounds 2a and 3 exhibited significant hPTP1B inhibitory activ-ity.