Here we show the use of branched peptides (i.e., isopeptides) as the substrates of proteases for generating supramolecular hydrogels via enzymatically clipping the branch off the peptides. As the first report of using a protease to cut branched peptides to enable a molecular process for converting nanostructures, this work illustrates a fundamentally new molecular motif for exploring the applications of protease-instructed self-assembly for soft materials.