The aim of this study was to develop controlled drug delivery by network scaffolds based on self-assembling peptide RADAFI and RADAFII. These two peptides self-assembled into interconnected nanofibrilar network structures with distinct physical morphologies. The hydrogels were also utilized for entrapment and release of some model guests, promising their future application as a drug delivery vehicle. Fickian diffusion controlled the release kinetics. Furthermore, the obtained release function was dependent on both rational design of the peptides used for hydrogel formation and choice of the entrapped molecules. On the basis of the striking different releases of these two peptide scaffolds, we suggested that guest size and lipophilicity influenced the release competitively. The release of RADAFI system was dominated by guest size, and the guest lipophilicity controlled the release behavior in RADAFII system. In a word, this work would potentially provide a spatially and temporally controlled delivery system for some functional drugs in the future.