Inspired by the antifouling properties of scaly fish, the conventional silicone coating with phenylmethylsilicone oil (PSO/PDMS) composite coating was fabricated and modified with single layer polystyrene (PS) microsphere (PSO/PDMS-PS) arrays. The fish scale like micro-nano structures were fabricated on the surface of bio-inspired coating, which can reduce the contact area with the secreted protein membrane of fouling organisms effectively and prevent further adhesion between fouling organisms and bio-inspired coating. Meanwhile, PSO exuded to the coating surface has the similar function with mucus secreted by fish epidermis, which make the coating surface slithery and will be polished with the fouling organisms in turbulent waters. Compared to PSO/PDMS coating without any structure and conventional silicone coating, PSO/PDMS-PS showed better antiadhesion activity against both marine bacteria and benthic diatom (Navicula sp.). Additionally, the existence of PS microspheres can reduce the release rate of PSO greatly, which will extend the service life of coating. Compared to PSO/PDMS coating, the sustained release efficiency of PSO/PDMS-PS coating can reach 23.2%. This facile method for fabricating the bio-inspired composite slow-release antifouling coating shows a widely fabricating path for the development of synergistic anti-fouling coating.