The aim of this study was to prepare and characterize zein and flavonoids of Houttuynia cordata (HCF) composite nanoparticles (NZH) and investigate the effects of different mass ratios of zein and HCF on the composite nanoparticles. The results showed that hydrogen bonding, hydrophobic and electrostatic interactions existed between HCF and zein, the melting temperature of NZH increased, and the thermal stability improved after the addition of HCF. With the increase of HCF, the average particle size and PDI of NZH first decreased and then increased, and the absolute value of zeta potential and encapsulation first increased and then decreased. Among them, NZH-3 (zein:HCF was 20:3) was homogeneous and well dispersed round spherical shape, the average particle size, the smallest PDI value, the narrowest particle size distribution peak, and the absolute value of zeta potential was the largest. In addition, the addition of HCF made the composite nanoparticles have higher DPPH. and ABTS scavenging ability. Compared with free HCF, NZH-3 had better heat treatment protection ability and improved the heating stability of HCF During the simulated gastrointestinal digestion, the HCF release rate of NZH-3 was only 22.31% after 120 min of digestion by SGF, and the sudden release phenomenon occurred in SIF digestion, and the HCF release rate reached 75.66% at 240 min of digestion by gastrointestinal fluid. NZH-3 release trends in the simulated gastrointestinal fluid were all consistent with the Ritger-Peppas model, but the release mechanisms were different, with a non-Fick diffusion mechanism in SGF and a Fick diffusion mechanism in SIF.