Protein engineering provides an opportunity to rationally combine self-assembly motifs with functional domains to create functionally active supramolecular structures. To this end, we have created self-assembling bioactive hydrogels through the fusion of previously developed hydrogel forming domains to functional proteins. Examples of monomeric (green fluorescent protein, GFP) and tetrameric (red fluorescent protein, DSRED) bioactive-hydrogel forming proteins are presented. Physical cross-linking of the protein monomers occurs due to the agglomeration of the alpha-helical hydrogel-forming domains into coiled-coils and also due to multimer formation. Small amplitude oscillatory shear experiments show that incorporation of the bioactive proteins into the hydrogel structure results in an increase in elastic character as judged by the storage modulus. Additionally, erosion rate is significantly suppressed as the incorporation of bioactive proteins impedes the formation of closed loops. Confocal microscopy and Förster Resonance Energy Transfer (FRET) experiments show that neat bioactive hydrogels and mixtures of the bioactive monomers and a previously designed protein hydrogel monomer are macrohomogenous. The compatibility of the hydrogel forming monomers also allows for the control of micro-scale structure, rheological properties and bulk bioactivity. This protein-engineering based approach to hydrogel design could prove to be a powerful means for constructing enzymatic and stimulus-responsive protein-based hydrogels for active scaffolds in tissue engineering applications and for surface modifications in bioreactor, biosensor and biofuel cell applications.