The utilization of layer-by-layer composite nanoparticles fabricated from zein and hyaluronic acid (HA) for the codelivery of curcumin and quercetagetin was investigated. A combination of hydrophobic effects and hydrogen bonding was responsible for the interaction of zein with both curcumin and quercetagetin inside the nanoparticles. Electrostatic attraction and hydrogen bonding were mainly responsible for the layer-by-layer deposition of hyaluronic acid on the surfaces of the nanoparticles. The secondary structure of zein was altered by the presence of the two nutraceuticals and HA. The optimized nanoparticle formulation contained relatively small particles ( d = 231.2 nm) that were anionic (ζ = -30.5 mV). The entrapment efficiency and loading capacity were 69.8 and 2.5% for curcumin and 90.3 and 3.5% for quercetagetin, respectively. Interestingly, the morphology of the nanoparticles depended on their composition. In particular, they changed from coated nanoparticles to nanoparticle-filled microgels as the level of HA increased. The nanoparticles were effective at reducing light and thermal degradation of the two encapsulated nutraceuticals and remained physically stable throughout 6 months of long-term storage. In addition, the nanoparticles were shown to slowly release the nutraceuticals under simulated gastrointestinal tract conditions, which may help improve their oral bioavailability. In summary, we have shown that layer-by-layer composite nanoparticles based on zein and HA are an effective codelivery system for two bioactive compounds.