Two novel cyclic tridecapeptides, tolybyssidins A (1) and B (2), were isolated from the culture medium of mass cultured cyanobacterium Tolypothrix byssoidea (EAWAG 195) by means of bioguided isolation. The gross structures of these peptides were determined by 1D and 2D NMR experiments and tandem mass spectrometry. Both peptides contain the nonnatural amino acid dehydrohomoalanine (Dhha) as well as proteinogenic amino acids albeit with D- or L-configuration. The compounds exhibit moderate antifungal activity against the yeast Candida albicans.