Hybrid self-assembly has become a reliable approach to synthesize soft materials with multiple levels of structural complexity and synergistic functionality. In this work, photoluminescent graphene quantum dots (GQDs, 2-5 nm) are used for the first time as molecule-like building blocks to construct self-assembled hybrid materials for label-free biosensors. Ionic self-assembly of disc-shaped GQDs and charged biopolymers is found to generate a series of hierarchical structures that exhibit aggregation-induced fluorescence quenching of the GQDs and change the protein/polypeptide secondary structure. The integration of GQDs and biopolymers via self-assembly offers a flexible toolkit for the design of label-free biosensors in which the GQDs serve as a fluorescent probe and the biopolymers provide biological function. The versatility of this approach is demonstrated in the detection of glycosaminoglycans (GAGs), pH, and proteases using three strategies: 1) competitive binding of GAGs to biopolymers, 2) pH-responsive structural changes of polypeptides, and 3) enzymatic hydrolysis of the protein backbone, respectively. It is anticipated that the integrative self-assembly of biomolecules and GQDs will open up new avenues for the design of multifunctional biomaterials with combined optoelectronic properties and biological applications.