To prevent the settlement and/or the growth of fouling organisms (i.e. bacteria, fungi or microalgae), benthic sessile species have developed various defense mechanisms among which the production of chemical molecules. While studies have mostly focused on the release of chemical compounds by single species, there exist limited data on multi-species assemblages. We used an integrative approach to explore the potential interactive effects of distinct assemblages of two corals species and one giant clam species on biofouling appearance and composition. Remarkably, we found distinct biofouling communities suggesting the importance of benthic sessile assemblages in biofouling control. Moreover, the assemblage of 3 species led to an inhibition of biofouling, likely through a complex of secondary metabolites. Our results highlight that through their different effect on their near environment, species assemblages might be of upmost importance for their survival and therefore, should now be taken into account for sustainable management of coral reefs.