Natural antifoulants have received significant interest in the search for non- or less-toxic antifouling coating systems for marine structures. Capsaicin, a natural compound that can be found in chili peppers, is known as an environmentally friendly antifouling agent with an excellent performance and a low environmental impact. However, controlling its release from the coating matrix is still an issue to be solved. With the aim of developing an eco-friendly antifouling system with prolonged long-term activity, in this study, we incorporated capsaicin in combination with dichlofluanid into water-based acrylic coating formulations. The antifouling activity of the resulting coatings was studied by examining the survival behavior of a Gram-negative marine bacterium Aeromonas Salmonoid ATCC 33658, and the release rate of capsaicin from the paint matrix was also assessed. The combination of 0.75 wt.% capsaicin and 0.75 wt.% dichlofluanid into the same matrix showed an antibacterial performance of up to 99.9% cfu reduction with an antibacterial value R 2.5–3 times higher than those obtained with the single biocides at 1.5 wt.%. The association between the two organic biocides created a synergistic effect on the antifouling performance, further resulting in a prolonged activity.