Echinoderms are unique sources of different metabolites having a wide spectrum of biological activities.All echinoderms possess a unique mechanism of decreasing the lever of free 5,6-unsaturated sterols in their cell membranes -sulfation of these food sterols. Moreover, sea cucumbers and starfish transform these 5,6-unsaturated sterols into stanols or 7,8-unsaturated sterols that allow them to synthesize and keep their own 5,6-sterol-depending membranolytic toxins, namely triterpene oligoglycosides for sea cucumbers and steroid olygoglycosides for starfish, which have protective significance for the producers. Starfish and brittle stars have numerous polyhydoxysteroids and their sulfated and glycosylated derivatives, using them as food emulgators.All echinoderms contain carotenoids and naphthoquinone pigments. The latter are widely presented in sea urchins. The lipid composition of echinoderms is also uncommon and very interesting. For example, they contain cerebrosides and gangliosides characteristic of other deuterostomes, including Chordata, Hemichordata, and Tunicata, relatives of echinoderms. Echinoderms contain lectins, glycan-specific glycoproteins with immunity functions for the producers, and glycoseaminoglycans.Microorganisms associated with some echninoderms and adopted into their toxins may also produce very uncommon metabolites, such as diterpene glycosides synthesized by some fungi associated with sea cucumbers. All the listed as well as other classes of echinoderm metabolites possess significant biomedical potential revealing cytotoxic, antitumor, antifungal, immunomodulatory, antioxidant activity, anti-arthritic, and anti-diabetic action and may also be used as a food supplement for nutrition. The main goal of this Special Issue, "Echinoderm Metabolites: Structure, Functions, and Biomedical Perspectives", is to provide a convenient platform for discussion of all possible scientific aspects concerning low molecular weight and biopolymer metabolites from echinoderms and the microorganisms associated with them, including their isolation and chemical structures, taxonomical distribution and participation in food chains, methods of analysis, biological activities, biosynthesis and evolution, biological functions, and chemical syntheses, including the obtaining of semi-synthetic derivatives of biologically active natural products.