Four new metabolites (1–4) have been isolated from the organic extract of the seagrass Cymodocea nodosa, collected at the coastal area of Porto Germeno, in Attica Greece. Compounds 1 and 2 belong to the structural class of diarylheptanoids, which have been found only once before in marine organisms [Kontiza, I.; Vagias, C.; Jakupovic, J.; Moreau, D.; Roussakis, C.; Roussis, V. Tetrahedron Lett. 2005, 46, 2845–2847]. Compound 3 is a new meroterpenoid, while compound 4, to the best of our knowledge, is the first briarane diterpene isolated from seaweeds, and only the second analog of this class with a tricyclic skeleton. Furthermore metabolite 4 is the first brominated briarane diterpene. The structures and the relative stereochemistry of the new natural products were established by spectral data analyses. The new metabolites were submitted for evaluation of their antibacterial activity against multidrug-resistant (MDR) pathogens including methicillin-resistant (MRSA) strains of Staphylococcus aureus, as well as the rapidly growing mycobacteria, Mycobacterium phlei, Mycobacterium smegmatis, and Mycobacterium fortuitum.