The development of stimuli-responsive materials in response to the molecules involved in biological processes has gained increased attentions. In this work, carboxymethyl chitosan (CM-chitosan) and poly(γ-glutamic acid) (pGlu) were reacted with a naturally occurring compound, genipin, leading to the formation of genipin-crosslinked CM-chitosan/pGlu conjugates with fluorescence emissions. The genipin-conjugated polymers were sensitive to the oxidation product of glucose, gluconic acid and hydrogen peroxide (H2O2). Fluorescence emissions of the polymers were quenched by gluconic acid and H2O2. An increase in the hydrodynamic diameter together with the quenching of fluorescence indicated that the genipin-conjugated polymers were self-aggregated into nanoparticles, in response to the stimulus of gluconic acid (but not for H2O2). Bovine serum albumin (BSA) could be loaded in the self-aggregated nanoparticles, and the incorporated BSA slowly released from the nanoparticles under hyper-gluconic acid conditions. This material is hence proposed as a stimuli-responsive material for optical sensing and protein delivery purposes.