Clathrate hydrates are among the most intensively studied H‐bond inclusion compounds. Despite the broad definition for this class of compounds, their meaning commonly refers to closed polyhedral nanocages that encapsulate small guest molecules. On the other hand, larger solutes enforce another type of encapsulation because of the solute size effect. Herein, we report a series of structures containing various molecules encapsulated by intercalated water layers constructed of polycyclic moieties of L4(4)8(8) topology. We parametrized the corrugation of individual layers and characterized interactions governing their formation. We suggested which could be categorized as two‐dimensional clathrates based on the character of intra‐layer interactions and effects observed between entrapped molecules and water‐based intercalators.