The combination of organic and inorganic components enables the development of new generation of materials with innovative applications in many fields. Clays are commonly used to confine different ions and molecules because they act as an engineering barrier, avoiding the release of the entrapped species. In this work, we have employed molecular dynamics simulations to study the diffusivity of a variety of organic molecules enclosed in the interlaminar space of clays. We have found that the diffusivity of confined organic molecules follows a universal trend, exhibiting low diffusion coefficients at low water contents, which are radically increased at a certain water content. This onset of diffusion is because of the rearrangement of the water molecules from monolayer to bilayer. At that point, the motion of the water/guest molecule clusters is decoupled, leading to the sharp increase of the diffusion coefficients.