The aim of this study was to physically modify zein (8–20% wt) using electrospraying (ESP) and to evaluate the changes in its morphology, chemical structure, and physical properties. The apparent viscosity and surface tension of zein solution affect the particles produced by ESP. The produced particles were spherical and in the sub-micron size (average size 2000 nm) and exhibited lower contact angle and surface hydrophobicity compared to commercial zein, which is attributed to changes in the secondary structure during processing. The addition of quercetin (0.1–0.4% wt), further improved the microstructure and interfacial properties. Wettability (6.24–17.86%) and interfacial tension of ESP-zein particles can be proportionally altered through the addition of quercetin. The molecular docking results suggest that hydrogen bonding and hydrophobic interactions exist between quercetin and zein, which may be responsible for the regulation of ESP-zein by quercetin. Such particles with tunable physical properties are strong candidates for the development of future food products.