The phycosphere—the chemical microenvironment surrounding phytoplankton—is a crucial hotspot for microbial exchange, driven by the secretion of small-molecule compounds. These exudates establish chemical gradients distinct from seawater, guiding chemoattractant bacteria. However, the specific chemical exchanges that facilitate these cross-kingdom interactions remain poorly understood. This study characterized the chemical basis of interactions between six cosmopolitan phytoplankton species (including diatoms, a dinoflagellate, a haptophyte, and a blue-green alga) and five pathogenic Vibrio species (V. alginolyticus, V. vulnificus, V. parahaemolyticus, V. mimicus, V. furnissii). We used settlement assays with cellular and supernatant extracts, sampled across three growth phases (exponential, stationary, decline), fractionating them into polar and non-polar components to determine their influence on bacterial colonization. The findings revealed "pro-Vibrio" chemicals in cellular extracts across all growth phases, with settlement-promoting activity peaking in the stationary phase. Polar intracellular compounds acted as chemoattractants for most Vibrio species, but notably excluded V. parahaemolyticus. Conversely, nonpolar intracellular extracts from P. tricornatum and A. cylindrica functioned as chemoinhibitors against V. parahaemolyticus, with P. tricornatum showing consistent inhibition across all stages. In the extracellular environment, polar chemicals from all three diatom species inhibited V. parahaemolyticus, while attracting other pathogenic Vibrio species. A chemoinhibition effect was also identified for V. vulnificus derived from A. cylindrica. These results demonstrate species-specific selectivity in Vibrio-phytoplankton interactions across different growth stages. This research underscores the ecological significance of these chemical exchanges, particularly as climate change increases the prevalence and geographic range of pathogenic Vibrio and associated diseases