Crystal engineering has proved to be an effective and reliable approach to tailor the physicochemical properties of active pharmaceutical ingredients. In this work, three novel sophocarpine salts were pre-pared and reported, named sophocarpine-hesperetin (SC-HES), sophocarpine-L-(-) malic acid monohy-drate (SC-LMA MH), and sophocarpine-p-hydroxybenzoic acid monohydrate (SC-PHBA MH). The crystal structures of the salts were confirmed by infrared spectroscopy and single crystal X-ray diffraction. SC-HES exhibited a laminated molecular stacking structure, SC-LMA MH formed a wavy layered structure, while sophocarpine molecules filled in the voids of the reticular structure to form the 3D structure of the SC-PHBA MH. Thermal analysis shows that after salification, the melting point of the compound in-creased from 78 degrees C to over 120 degrees C, overcoming its low melting point. Lattice energy and Hirshfeld surface analysis indicated that lower lattice energy provides better thermal stability of the crystal and intermolec-ular hydrogen bonds (O-H middotmiddotmiddotO and N -> H middotmiddotmiddotO) play a key role in the construction of the crystal structures. In addition, the water solubility and hygroscopicity of the three salts were characterized and discussed, with SC-HES exhibiting satisfying physical stabilities and hygroscopicity, and SC-LMA MH achieving 6.7 times solubility than the free base, which provides viable options for solid dosage form development of the drug.(c) 2023 Elsevier B.V. All rights reserved.