Dermal exposures to hazardous environmental chemicals in water can significantly affect the morphology and integrity of skin structure, leading to enhanced and deeper penetration. Organic solvents, such as benzene, toluene, and xylene (BTX), have been detected in humans following skin exposure. In this study, novel barrier cream formulations (EVB™) engineered with either montmorillonite (CM and SM) or chlorophyll-amended montmorillonite (CMCH and SMCH) clays were tested for their binding efficacy for BTX mixtures in water. The physicochemical properties of all sorbents and barrier creams were characterized and were shown to be suitable for topical application. In vitro adsorption results indicated that EVB-SMCH was the most effective and favorable barrier for BTX, as supported by the high binding percentage (29–59% at 0.05 g and 0.1 g), stable binding at equilibrium, low desorption rates, and high binding affinity. Pseudo-second-order and the Freundlich models best fit the adsorption kinetics and isotherms, and the adsorption was an exothermic reaction. Ecotoxicological models usingL. minorandH. vulgaristhat were submersed in aqueous culture media showed that the inclusion of 0.05% and 0.2% EVB-SMCH reduced BTX concentration. This result was further supported by the significant and dose-dependent increase in multiple growth endpoints, including plant frond number, surface area, chlorophyll content, growth rate, inhibition rate, and hydra morphology. The in vitro adsorption results and in vivo plant and animal models indicated that green-engineered EVB-SMCH can be used as an effective barrier to bind BTX mixtures and interrupt their diffusion and dermal contact.