Background <p>Jellyfish blooms pose a serious threat to marine ecosystems and coastal socio-economic activities, requiring urgent development of control technologies to manage harmful jellyfish. Associated bacteria hold considerable importance in the growth and development of marine invertebrates. We isolated <i>Bacillus pacificus</i> SG15 from the seagrass rhizosphere and observed that this strain could inhibit the asexual reproduction of the jellyfish <i>Aurelia coerulea</i> polyp. However, the precise interaction processes underlying this inhibition remain unclear. Therefore, we aimed to elucidate these processes by performing a coculture experiment coupled with analyses utilizing high-throughput sequencing, transcriptomics, metabolomics, and fluorescence <i>in situ</i> hybridization.</p> Results <p>Our findings indicate that the transcription of genes involved in the absorption of vitamins B5, B11, B12, C and biotin was inhibited with SG15 treatment despite relatively high concentrations of vitamins and their derivatives in the culture medium. SG15 treatment increased the levels of carbohydrate metabolism genes, including those involved in pyruvate metabolism, glycolysis/gluconeogenesis, pentose phosphate pathways, and citrate cycle metabolites. Furthermore, SG15 influenced both endodermal and ectodermal polyp cells.</p> Conclusions <p>Collectively, our findings helped elucidate the interactions between associated bacteria and polyps and the process by which <i>B. pacificus</i> SG15 inhibits polyp asexual reproduction, providing novel insights into the role of bacteria in the development of marine invertebrates. This study could provide a theoretical framework and empirical evidence for the biological control of jellyfish blooms in the marine aquaculture area, which may help develop strategies aimed at mitigating the impacts of jellyfish blooms on marine ecosystems and coastal communities.</p>