The settlement and growth of fouling organisms on man-made surfaces can be prevented by the application of antifouling paints containing active compounds (biocides, heavy metals), most of which are toxic to non-target organisms. As part of our research program in chemical ecology and blue biotechnology, we are conducting studies to investigate the natural defence mechanisms of marine organisms that are free from epibionts, with the aim of isolating molecules involved in surface defence that could be good candidates as antifouling agents. Ascidians were selected for our investigation because previous studies have shown that they contain abundant and diverse secondary metabolites, which play a defensive role and have been applied to drug discovery. It is therefore relevant to study the role of such secondary metabolites in surface protection. In this study, 5 meroterpenoids (cordiachromene A, didehydroconicol, epiconicol, methoxyconidiol, conidione) from Aplidium aff. densum (ascidian) were investigated as potential antifoulants towards the inhibition of bacterial growth and settlement inhibition of barnacles. Cardiochromene A (IC50 barnacle settlement = 6.04 μg/mL; MIC Gram positive = 125 μg/mL; MIC Gram negative = 32 μg/mL) and epiconicol (IC50 barnacle settlement = 8.05 μg/mL; MIC Bacillus = 63 μg/mL; MIC other strains = 32 μg/mL) were the most promising compounds among those tested in this study.