Peperomia duclouxii (Piperaceae) mainly grows in Yunnan, Guangxi, Guangdong and Fujian Provinces of China and is used as anti-cancer agent. There has been no report on its chemical constituents. In order to establish the bioactive compounds, we investigated the constituents of P. duclouxii. Ten new lignans (including 5 dibenzylbutyrolactones, 2 dibenzylbutanediols, 1 diaryltetrahydrofuran and 2 furofuran lignans) were obtained from the ethyl acetate extract and their structures were elucidated by extensive NMR and MS spectra and the absolute configurations were established by optical rotations and CD spectra. The CNS (central nervous system) activities of 1, 3, 5 and 6 are in progress. These isolated lignans indicated that the similar biosynthetic pathway with that in Forsythia maybe exists in P. duclouxii: furofuran lignans (4 or 7) →→ dibenzylbutanediol lignans (2 or 6)→dibenzylbutyrolactone lignans (1 or 5). But the absolute configuration of the starting point (-)-4 and/or (-)-7 was opposite that of (+)-pinoresinol, and the absolute configurations of the reduction and oxidation products (+)-2, (+)-6, (+)-1, (+)-5 were also opposite those of (-)-secoisolariciresinol, (-)-matairsinol, so maybe some other specific enzymes act on this procedure. It will also need more investigation whether the intermediate diaryltetrahydrofuran lignan exist in this procedure, because only (+)-3 was obtained whereas the intermediate should be (-)-3 according to our proposed biosynthetic procedure. Whatever, these results showed that the stereoselectivities of the biosynthesis procedure in P. duclouxii are different with those in Forsythia and most of other plants, and the mechanisms are worth researching. Compounds 8, 9 and 10 were the oxidation products of 5.