Halicylindramides D (1) and E (2) have been isolated from the marine sponge Halichondria cylindrata. Halicylindramide D is a tridecapeptide with the N-terminus blocked by a formyl group and the C-terminus lactonized with a threonine residue, while halicylindramide E is a truncated linear peptide with a C-terminal amide. Their structures, including absolute stereochemistry, were determined by a combination of spectral and chemical methods. Halicylindramide D was antifungal against Mortierella ramanniana and cytotoxic against P-388 murine leukemia cells.