Abstract A simple, straightforward, and highly efficient greener approach for synthesizing bis(6‐aminouracil‐5‐yl)methane derivatives was developed by employing β‐cyclodextrin‐SO 3 H as supramolecular catalyst in water at 100 °C. A total of 16 bis(6‐aminouracil‐5‐yl)methanes were synthesized via a one‐pot reaction between substituted aromatic aldehydes, 6‐amino‐1,3‐dimethyluracil, and 10% β‐cyclodextrin‐SO 3 H in water with 84%–92% yield within 20–120 min. The salient features of this protocol included water as green solvent, β‐cyclodextrin‐SO 3 H as recyclable supramolecular catalyst, mild reaction conditions, easy isolation of pure products, and good to excellent yields.