Six new dibenzylbutyrolactone (6-11) and two new dibenzylbutanediol lignans (12, 13) were obtained from Peperomia duclouxii. The structures were elucidated mainly by the analysis of NMR and MS data. The anticancer activity against a normal (WI-38) and a simian virus 40-transformed human lung fibroblast cell (VA-13) and a hepatoma G2 cell (HepG2) and the MDR reversal activity of the isolated compounds were examined. Compound 7 showed moderate inhibitory activity against VA-13 and HepG2 with IC(50) values of 23.2 and 26.4 microM, respectively. Compound 2 inhibited the growth of HepG2 cells with an IC(50) of 42.8 microM. Compounds 2 and 13 exhibited stronger MDR reversal activity than verapamil, at 25 and 2.5 microg/mL, respectively, and 4, 5, and 7 showed comparable activity with verapamil, at 25, 25, and 2.5 microg/mL, respectively.