The chapter on marine biodiversity and bioprospecting in Vietnam provides coverage on the taxonomic diversity and distribution as well as range of specialized metabolites reported from benthic marine invertebrates, including sponges, cnidarians and echinoderms. An analysis of the marine biodiversity across Vietnam’s coastal regions, with a focus on sponges, octocorals and echinoderms, will be presented. A total of 291 sponge species have been recorded, predominantly from the class Demospongiae, while extensive surveys reveal diverse octocoral species (220 species, 48 genera) concentrated in the Southeast Coastal Region. Echinoderm diversity is also high, with 345 species documented across five main classes, especially in the Southeast region. Hierarchical clustering and MDS analyses reveal distinct biogeographic patterns, showing close species composition similarity between the Southwest and Southeast regions, while the North Central region maintains unique species characteristics. These biodiversity patterns suggest the influence of ecological and environmental factors on species distribution, highlighting the critical importance of these regions in supporting Vietnam’s rich marine ecosystems. In addition, the chapter covers marine natural products derived from these marine invertebrates reported in literature from 1990 to 2023. It includes discussion on synthetic efforts and molecular targets of selected molecules as drug leads for biomedical applications.