A pharmacological screening of the ethanol extract and fractions of two Peruvian medicinal plants, Plagiochila disticha and Ambrosia peruviana, led to the isolation and characterization of three ent-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline A (1), I (2), and R (3), as well as of two pseudoguaianolids, damsin (4) and confertin (5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 1, 4, and 5 were also investigated for their in vitro antileishmanial, trypanocidal, and antituberculosis activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes, as well as against MDR and sensitive strains of Mycobacterium tuberculosis, respectively. © Georg Thieme Verlag KG Stuttgart.