Water-dispersible curcumin nanoparticles were prepared by bottom-up antisolvent precipitation approach. A new high-throughput screening technique was developed for selecting appropriate ligands stabilizing the nanoparticles in aqueous medium and improving their performance. The initial set of twenty-eight potential stabilizing ligands was evaluated based on their capacity to improve curcumin dispersibility in aqueous medium. The performance of four promising ligands(amino acid proline, polyphenol tannic acid, polycation Polyquaternium 10, and neutral polymer polyvinylpyrrolidone) was tested in ultrasound-aided antisolvent precipitation trials. Using the selected stabilizing ligands diminished the average particle size from ca. 1,200 to 170–230 nm, reduced their dispersity, improved stability, and allowed reaching curcumin concentration of up to 1.4 m M in aqueous medium. Storage stability of the aqueous nanodispersions varied from 2 days to 2 weeks, depending on stabilizing ligand. Studying the effects of ionic strength and pH on size and f-potential of the particles suggested that electrostatic forces and hydrophobic interactions could be the major factors affecting their stability. The ligand-protected nanoparticles showed minimal inhibitory concentration of 400 or500 μM toward Escherichia coli. We suggest that the presented screening approach may be useful for preparing nanoparticles of various poorly water-soluble bioactive materials. Water-dispersible curcumin nanoparticles were prepared by bottom-up antisolvent precipitation approach. A new high-throughput screening technique was developed for selecting appropriate ligands stabilizing the nanoparticles in aqueous medium and improving their performance. The initial set of twenty-eight potential stabilizing ligands was evaluated based on their capacity to improve curcumin dispersibility in aqueous medium. The performance of four promising ligands (amino acid proline, polyphenol tannic acid, polycation Polyquaternium 10, and neutral polymer polyvinylpyrrolidone) was tested in ultrasound-aided antisolvent precipitation trials. stabilizing ligands diminished the average particle size from ca. 1,200 to 170-230 nm, reduced their dispersity, improved stability, and allowed reaching reaching curcumin concentration of up to 1.4 m M in aqueous medium. Storage stability of the aqueous nanodispersions varied from 2 days to 2 weeks, depending on stabilizing ligand. S tudying the effects of ionic strength and pH on size and f-potential of the particles suggests that electrostatic forces and hydrophobic interactions could be the major factors affecting their stability. The ligand-protected nanoparticles showed minimal inhibitory concentration of 400 or 500 μM toward Escherichia coli. We suggest that the presented screening approach may be useful for preparing nanoparticles of various poorly water-soluble bioactive materials.