The investigation of Xylaria ianthinovelutina (Mont.) led to the isolation of four new 12,8-eudesmanolides (1–4). Their structures were determined by spectroscopy and the relative stereochemistry was assigned based on NOESY and CD spectral data. Compounds 1–4 exhibited biological activity against Plasmodium falciparum K-1 strain, NCI-H187, KB, MCF-7 with IC50 values varying in the range 0.78–19.15 µg/mL.