Honokiol (HK), a BCS class II drug with a wide range of pharmacological activities, has poor solubility and low oral bioavailability, severely limiting its clinical application. In the current study, incorporating a water-soluble meglumine (MEG) into the crystal lattice of HK molecule was performed to improve its physicochemical properties. The binary mixture of HK and MEG was obtained by anti-solvent method and characterized by TGA, DSC, FTIR, and PXRD. The SCXRD analysis showed that two HK- molecules and two MEG+ molecules were coupled in each unit cell via the ionic interaction along with intermolecular hydrogen bonds, suggesting the formation of a salt, which was further confirmed by the XPS measurements. However, the ∆pKa value between HK and MEG was found to be less than 1, which did not follow the oft-quoted ∆pKa rule for salt formation. After salification with MEG, the solubility and dissolution rate of HK exhibited 3.50 and 25.33 times improvement than crystalline HK, respectively. Simultaneously, the powder flowability, tabletability and stability of HK-MEG salt was also significantly enhanced, and the salt was not more hygroscopic, and that salt formation did not compromise processability in that regard. Further, in vivo pharmacokinetic study showed that Cmax and AUC0-t of HK-MEG salt were enhanced by 2.92-fold and 2.01-fold compared to those of HK, respectively, indicating a considerable improvement in HK oral bioavailability.