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Smart biocompatible materials that respond to a variety of external stimuli have a lot of potential in the creation of low-cost diagnostic biosensors. The present work describes the creation of core–shell nanoparticles as a biosensor for smart enzyme detection of salivary alpha-amylase (sAA). A chitosan-tripolyphosphate core was generated via ionic gelation and was coated with a starch–iodine shell to create biocompatible core–shell nanoparticles. The starch–iodine shell was ruptured in the presence of certain amounts of amylase, exposing the core. This application explains a noticeable color change from blue to white that can be used to identify sAA at the point of care. Synthesized nanoparticles were examined for scanning electron microscopy analysis and energy-dispersive X-ray (EDX). An EDX report reveals that the nanoparticles have higher carbon content at 55% followed by an oxygen atom of 35%. Fourier-transform infrared spectroscopic analysis revealed that the core–shell nanoparticles have carbonyl (C═O) functional groups present. A confirmatory test of amylase reaction on nanoparticle-impregnated paper turns blue to white indicating that the nanoparticle reacts with amylase as an indicator. This paper-based method can be used in future applications in forensic and medical applications. [ABSTRACT FROM AUTHOR]