With the recent development of state-of-the-art technologies (e.g hyphenated MS techniques) and methodologies (e.gdereplication), the scientific community is interested in the exploration of poorly chemically studied bioresources. The high diversity of interacting phytoplankton species suggests an important and highly diverse chemical repertoire (e.gisoprenoids, toxins, polysaccharides, PUFAs, oxylipins, phycobiliproteins) which may inspire applications in health, nutrition and biotechnology. Biosynthesis of these metabolites is strongly dependent upon their environment/culture conditions which may be investigated using OMICS approaches. In microalgae, a major bottleneck isthe difficulty in extracting deeply inaccessible molecules, an important issue that demands adapted solutions prior to considering High-Throughput Screening (HTS). Bioactive minority metabolites may pass unnoticed on spectra and thus require special attention. The extraction of metabolites may prove difficult due to the presence of highly resistant cell walls (Phaeodactylumtricornutum), or of exopolysaccharidic secretions surrounding the cell membrane (Porphyridiumpurpureum). The Mix Mill process (vibrating microbeads) which gave excellent extraction yields without chemical alteration of the analytes) and is fully compatible with HPLC and LC-MS analysis was optimised. Being accurate, simple to operate, rapid, safe and preserving sensitive molecules, makes the Mix Mill process suitable for the screening of microalgalchemodiversity. This methodology was applied in the Photomer, and currently in OCEANOMICs and OCEANCHArCoT programs, all being dedicated to the identification of new marine metabolites with high added value. Finally, this methodology represents a significant improvement in the field of OMICS studies from microalgae, as it provides the most representative estimate of their exploitable chemical diversity.