The investigation of the chemical constituents from the roots of Psacalium radulifolium, a member of the matarique complex of medicinal plants, which includes several members of the Asteraceae, resulted in the isolation of four new modified eremophilanes: radulifolin A (4), epi-radulifolin A (5), radulifolin B (6), and radulifolin C (7), together with the known natural substances cacalol, cacalone, epi-cacalone, O-methyl-1,2-dehydrocacalol, adenostin A, decompostin, and neoadenostylone. Antimicrobial evaluation of the extracts and the isolated compounds indicated that cacalol was the major active compound.