Antifoulant paints were developed to prevent and reduce biofouling on surfaces immersed in seawater. The widespread use of these substances over the years has led to a significant increase of their presence in the marine environment. These compounds were identified as environmental and human threats. As a result of an international ban, research in the last decade has focused on developing a new generation of benign antifoulant paints. This review outlines the detrimental effects associated with biocide versus eco-friendly antifoulants, highlighting what are effective antifoulants and why there is a need to monitor them. We examine the effects of biocide and eco-friendly antifoulants on the antioxidative defence mechanism and settlement in a higher sessile organism, specifically the Mediterranean mussel, Mytilus galloprovincialis. These antifoulants can indirectly assess the potential of these two parameters in order to outline implementation of sustainable antifoulants.