The most efficient catalysts have been developed and optimized by living systems. Indeed, in vivo enzyme-catalyzed reactions are several orders of magnitude more efficient than platinum-based catalyzed reactions. However, the rate of reaction and equilibrium interactions are considerably reduced when the biological systems are studied in vitro. This phenomenon is largely attributed to the effect of confinement or macromolecular crowding present in the cell. This paper focuses on the effect of the confinement in nanotemplates by decoupling the different factors that could influence the polymerization reaction of pyrrole within the templates. Indeed, the effect of the chemistry of the template, the size of the confinement, and in a previous study the contact with water are investigated separately. It is shown that the effect of confinement is paramount in the environmentally-friendly polymerization of pyrrole within nanotemplates.