<jats:sec> <jats:title>Abstract</jats:title> <jats:p>Marine dissolved organic matter (DOM) comprises a vast and unexplored molecular space. Most of it resided in the oceans for thousands of years. It is among the most diverse molecular mixtures known, consisting of millions of individual compounds. More than 1 Eg of this material exists on the planet. As such, it comprises a formidable source of natural products promising significant potential for new biotechnological purposes. Great emphasis has been placed on understanding the role of DOM in biogeochemical cycles and climate attenuation, its lifespan, interaction with microorganisms, as well as its molecular composition. Yet, probing DOM bioactivities is in its infancy, largely because it is technically challenging due to the chemical complexity of the material. It is of considerable interest to develop technologies capable to better discern DOM bioactivities. Modern screening technologies are opening new avenues allowing accelerated identification of bioactivities for small molecules from natural products. These methods diminish a priori the need for laborious chemical fractionation. We examine here the application of untargeted metabolomics and multiplexed high-throughput molecular-phenotypic screening techniques that are providing first insights on previously undetectable DOM bioactivities.</jats:p> </jats:sec><jats:sec> <jats:title>Key points</jats:title> <jats:p>• <jats:italic>Marine DOM is a vast, unexplored biotechnological resource.</jats:italic></jats:p> <jats:p>• <jats:italic>Untargeted bioscreening approaches are emerging for natural product screening.</jats:italic></jats:p> <jats:p>• <jats:italic>Perspectives for developing bioscreening platforms for marine DOM are discussed.</jats:italic></jats:p> </jats:sec>