Enzymes are natural catalysts that are composed of highly ordered proteins and provide nanostructured active sites for specific reactions. The ability of enzymes to efficiently bind substrates in aqueous environments and spontaneously release products upon reaction completion has inspired the development of synthetic catalysts (enzyme mimetics) based on well-organized supramolecular nanomaterials. The amphiphilicity of these materials can be exploited to dissolve hydrophobic substrates in polar solvents and gather such substrates in the hydrophobic confined spaces of supramolecular cavities. The result is high local concentrations of substrates, which allows organic reactions to proceed in polar solvent environments. Supramolecular materials can also reversibly change their functions and structures in response to external stimuli such as temperature, solvents, and guest molecules to realize the on/off switching of supramolecular catalyst-promoted reactions. In this Perspective, we introduce supramolecular materials produced by the self-assembly of aromatic amphiphiles and discuss their applications as catalysts for various reactions in polar solvents. Furthermore, we highlight the potential of these materials and provide insights into the related next-generation catalysts.