Accidents with toxic industrial chemicals and threats posed by chemical warfare agents, as organophosphorus nerve agents and blistering agents, has become an increasing concern over the last decades. Intoxication is not only due to inhalation but dermal route can also be important and can quickly lead to death. It is therefore crucial to have suitable means of personal protection and decontamination. Some are already commercially available but often present drawbacks. Efforts have been made to develop new systems and several studies have shown the interest of metallic nanoparticles. The challenge remains to entrap the particles in an adapted matrix to limit their diffusion in the immediate environment, while preserving the bare particles decontamination efficacy. In this study, an easy to handle peelable gel, incorporating CeO₂ nanoparticles has been developed for efficient skin decontamination against toxic chemicals. The main objective has been to make it suitable in any context of application (battlefield or civil exposure). Nano-octahedra (NO) CeO₂ particles synthetized in this study have been able to increase the degradation of paraoxon, a simulant warfare agent in liquid media. NO have then been incorporated in a peelable gel, the formulation has been optimized through design of experiments and its physico-chemical properties characterized. Even after incorporation to the gel, NO retained their neutralization properties. The formulation efficiency towards neutralization and skin decontamination have been evaluated in vitro on Franz diffusion cells. The interest of the peelable gel have been clearly demonstrated with a decrease by about 5-fold of the quantity of POX absorbed into the skin and a decrease of 3–4-fold in the viable skin, which was much higher than the use of cotton or nanoparticles as powder.