A new amphiphile 1a featuring with two ‐NHSO2C4F9 sites is designed and synthesized as Brønsted diacid. The amphiphilicity arose from nano‐aggregations of hydrophobic fluorocarbon chains and extension of hydrophilic NH groups, confirmed by Tyndall effect and TEM. The acidity of 1a rivals to concentrated H2SO4, examined by the Hammett acidity function, 31P NMR and conductance titration. Compound 1a demonstrated excellent catalytic performance in the Friedel–Crafts alkylation of indoles in water. Reactive substrates, such as β‐monosubstituted vinyl ketones in 1,4‐addition and aldehydes in condensation, were quantitatively converted, and the products were easily isolated by filtration or extraction in 85–96 % yields. Additionally, there was no observation of effect of the acidity weakening of 1a on catalysis when poor‐reactive substrates were used, such as β,β‐disubstituted vinyl ketones in 1,4‐addition and ketones in condensation. The two kinds of reactions were practised very smoothly. The formed nano‐aggregations and the strong acidity of 1a were responsible for the highly efficient aqueous catalysis. Notably, 1a was recycled at least 3 times thanks to its amphiphilic structure. It was demonstrated the nano‐aggregations played a key role in the aqueous synthesis.