Polyamine–salt aggregates (PSA) are biomimetic soft materials that have attracted great attention due to their straightforward fabrication methods, high drug‐loading efficiencies, and attractive properties for pH‐triggered release. Herein, a simple and fast multicomponent self‐assembly process was used to construct cross‐linked poly(allylamine hydrochloride)/phosphate PSAs (hydrodynamic diameter of 360 nm) containing glucose oxidase enzyme, as a glucose‐responsive element, and human recombinant insulin, as a therapeutic agent for the treatment of diabetes mellitus (GI‐PSA). The addition of increasing glucose concentrations promotes the release of insulin due to the disassembly of the GI‐PSAs triggered by the catalytic in situ formation of gluconic acid. Under normoglycemia, the GI‐PSA integrity remained intact for at least 24 h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4 h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose‐responsive delivery nanocarriers.