The development of nanoparticle-based delivery systems has revolutionized the field of food science and nutrition, offering innovative solutions to enhance the bioavailability and stability of bioactive compounds. However, the poor water solubility and low bioavailability of some bioactive molecules (e.g., quercetin), which are easily degraded under the harsh conditions of the gastrointestinal tract, have hindered their practical application in functional foods. This study elucidates the formation of digestive enzyme coronas on quercetin-loaded starch nanoparticles (QSNP) and their functional consequences during simulated digestion. SEM revealed the size of specific enzymes corona on QSNP: 220.6 ± 2.2 nm (α-amylase), 256.0 ± 8.6 nm (pepsin), 291.7 ± 5.7 nm (trypsin) and 218.5 ± 3.1 nm (lipase). Corresponding zeta potential shifts were observed, most notably from -18.1 ± 1.4 mV to -11.2 ± 0.3 mV for alpha-amylase-treated QSNP. FTIR and circular dichroism spectroscopy showed that enzyme adsorption altered the surface chemistry and secondary structure of the QSNP, with α-amylase preferentially hydrolyzing the amorphous starch region, while trypsin and lipase formed bile salt-stabilized coronas. Most importantly, the enzyme coronas differentially regulate digestive activity: α-amylase is inhibited (16.14% residual activity), whereas lipase activity is increased (4-fold relative activity) due to interface activation. The release kinetics of quercetin were correlated with the corona component, showing Fickian diffusion (α-amylase, n = 0.43), first-order (trypsin), and erosion-control (lipase) mechanisms. These findings mechanistically reveal how enzyme-specific corona structures determine the behavior of starch nanoparticles during digestion, providing a rational design strategy for controlled-release nutraceutical delivery systems.