We report the preparation of biocompatible, dual stimuli-sensitive lipoic acid-modified poly(l-lysine) (PLL-g-Lipo) hydrogels/nanogels by chemical cross-link and polypeptide/silica hybrid hydrogels/nanogels by simply depositing silica in the gel matrix. Hydrogels were prepared by ethylene oxide sterilization through the formation of inter-/intramolecular disulfide cross-link. Their gelation and mechanical properties were dictated by the degree of inter-/intramolecular disulfide cross-link and amphiphilic nature, which was influenced by the chain conformation. These hydrogels exhibited reduction- and pH-sensitive properties as demonstrated by the accelerated drug release upon changing the solution pH from neutral to acidic condition and/or cleaving disulfide bonds. Swelling studies demonstrated that the genipin and disulfide cross-linked nanogels prepared by miniemulsion exhibited redox- and pH-sensitive properties. Silica deposition resulted in hybrid nanogels exhibiting excellent colloid stability. Silica deposition can not only stabilize the gel network but also tune their mechanical properties as well as their payload release and colloidal properties.