A novel approach is presented to create self-assembling hydrogels. Microspheres based on cross-linked dextran were chemically modified with L- or D-oligolactate chains. Successful grafting of the particles was confirmed by Fourier transform infrared (FT-IR) and Raman and X-ray photoelectron spectroscopy (XPS). Rheological analysis of aqueous dispersions of oligolactate-grafted microspheres demonstrated that hydrophobic interactions between oligolactate chains on the surface of various microspheres resulted in the formation of an almost fully elastic gel. A mixture of microspheres substituted with L- or D-oligolactates of opposite chirality resulted in gels with highest strength, likely due to stereocomplexation between the enantiomers. The network properties could be modulated by varying the solid content of the gel, the DS (i.e., number of lactate grafts per 100 glucopyranose units) and the DP (i.e., degree of polymerization) of the oligolactate grafts. Protein loading of the hydrogels could be achieved by simply mixing the microspheres with protein solution. Release experiments showed a continuous release of the entrapped lysozyme, with 50% released after 5 days and full preservation of its enzymatic activity. The biocompatible nature of the material, the protein-friendly self-assembly of the hydrogel and the possibility to tailor the gel properties, makes this hydrogel system an attractive candidate for pharmaceutical and biomedical applications.