Taking inspiration from natural systems, such as spider silk and mollusk nacre, that employ hierarchical assembly to attain robust material performance, we leveraged matrix-filler interactions within reinforced polymer-peptide hybrids to create self-assembled hydrogels with enhanced properties. Specifically, cellulose nanocrystals (CNCs) were incorporated into peptide-polyurea (PPU) hybrid matrices to tailor key hydrogel features through matrix-filler interactions. Herein, we examined the impact of peptide repeat length and CNC loading on hydrogelation, morphology, mechanics, and thermal behavior of PPU/CNC composite hydrogels. The addition of CNCs into PPU hydrogels resulted in increased gel stiffness; however, the extent of reinforcement of the nanocomposite gels upon nanofiller inclusion also was driven by PPU architecture. Temperature-promoted stiffening transitions observed in nanocomposite PPU hydrogels were dictated by peptide segment length. Analysis of the peptide secondary structure confirmed shifts in the conformation of peptidic domains (α-helices or β-sheets) upon CNC loading. Finally, PPU/CNC hydrogels were probed for their injectability characteristics, demonstrating that nanofiller-matrix interactions were shown to aid rapid network reformation (∼10 s) upon cessation of high shear forces. Overall, this research showcases the potential of modulating matrix-filler interactions within PPU/CNC hydrogels through strategic system design, enabling the tuning of functional hydrogel characteristics for diverse applications.