Biofouling poses a significant challenge to the marine industry, resulting from the undesirable accumulation of various living organisms, including microorganisms, plants, shellfish, and others, on different surfaces submerged in seawater. The primary approach to address this issue involves the application of antifouling coatings, often incorporating active agents whose environmental impact has raised considerable concerns. In this article, we compare the effects of two natural and environmentally friendly antimicrobial compounds, capsaicin (CP) and Cinnamomum cassia oil (CO), when incorporated into hybrid sol–gel coatings. We tested formulations containing 4% and 8% by weight of each biocide for coating nylon substrates through immersion. This process yielded colorless, uniform surfaces with minimal defects and strong adhesion. We evaluated the antibacterial properties of the pure organic biocides against five bacterial strains commonly found in Chilean microfouling. Both compounds exhibited similar behavior against Gram-positive bacteria, but CP showed 2–5 times greater efficacy than CO against Gram-negative strains. Subsequently, we selected a Gram-negative strain for antibacterial tests on sol–gel/biocide samples. The results indicated that coatings with CP incorporation outperformed those with CO, achieving an efficiency of 99.9%. Lastly, leaching tests demonstrated that coatings with lower biocide concentrations (4%) exhibited a steady and gradual release of organic molecules, with sol–gel/CP 4% emerging as the most promising microfouling barrier coating for marine applications.