Glabridin (Gla) is a natural active ingredient extracted from licorice root with good whitening activity. However, its poor solubility limits its further application. Therefore, this study aimed to develop a novel co-amorphous Gla–OMT raw material using oxymatrine (OMT) as a co-former, aiming to improve its physicochemical properties and enhance its whitening activity. Firstly, the formation of co-amorphous Gla–OMT was confirmed by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Subsequently, FT-IR, NMR, and molecular dynamics simulations were used to investigate the interaction between the co-amorphous Gla–OMT molecules, and solubility experiments and supersaturation dissolution experiments were used to investigate the solubilization of the co-amorphous Gla–OMT. In addition, the in vitro release mechanism of the co-amorphous Gla–OMT was investigated using a Franz diffusion cell and its biosafety and whitening activity were evaluated using cell experiments. In conclusion, the successful preparation of co-amorphous Gla–OMT and the evaluation of its whitening activity in this study have significant implications for guiding the development and application of whitening products in the future.