The properties of zein nanoparticles formed by anti-solvent precipitation are affected by solvent type, solvent composition, mixing method, and dilution ratio. Ultrasound is a non-thermal technology and can be used to assist in the fabrication of zein nanoparticles. Curcumin is a natural bioactive compound that has health benefits for humans. The objectives of this study were 1) to evaluate the effect of ethanol concentration, the ratio of the dispersed phase to continuous phase, and the amplitude of ultrasound on the properties of zein nanoparticles and 2) to assess the encapsulation and stability of curcumin in the zein nanoparticles via ultrasonic treatment. Zein nanoparticles were fabricated by ultrasonic treatment with various initial ethanol concentrations in the continuous phase, volume ratios of the dispersed to continuous phases, and ultrasound amplitudes. The particle size decreased as the concentration of ethanol in the continuous phase decreased. Curcumin was encapsulated by selected ultrasonic treatments and the particle size, encapsulation efficiency, and XRD of zein-curcumin nanoparticles were analyzed. The findings from this study provide insights and means for manipulating zein nanoparticles by adjusting processing conditions when using ultrasound. Also, encapsulation of bioactive compounds such as curcumin can be improved using controlled ultrasound treatment. •Zein nanoparticles were fabricated by ultrasonic treatment with various ratios of dispersed phase to continuous phase.•Zein-curcumin nanoparticles were fabricated by ultrasonic treatment with different initial ethanol concentrations.•The particle size increased as the ethanol concentration in the continuous phase increased.•The encapsulated curcumin was more stable toward heat and light than free curcumin.•At critical ethanol concentration, the nanoparticle formation and curcumin encapsulation changed significantly.