Purpose: To address the challenges of low water solubility and poor bioavailability of quercetin (QUE), which limit its clinical application, and to develop an optimized oral solid dispersion formulation to enhance its absorption. Methods: Quercetin solid dispersions (QUE-SD) were prepared using the solvent evaporation method. The study involved screening single-factor and combined carriers, followed by formulation optimization via orthogonal analysis based on solubility and cumulative dissolution rates. The optimized dispersions were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Additionally, transmembrane transport was evaluated using Caco-2 and MDCK cell models, and oral bioavailability was assessed through pharmacokinetic studies in rats. Results: The optimal formulation was determined to be a 1:3:1 ratio of Quercetin, Hypromellose E5, and polyvinylpyrrolidone K13-18, with an evaporation temperature of 55 °C and a mixing time of 4 h. In cell transport models, the apparent permeability coefficient of QUE-SD increased by 1.14 (Caco-2) and 1.1 (MDCK) times. Pharmacokinetic data confirmed that the solid dispersion significantly improved both the absorption rate and oral bioavailability of quercetin in rats. Conclusions: The prepared quercetin solid dispersion effectively enhances the water solubility, transmembrane transport, and systemic absorption of quercetin. These findings provide a viable strategy and theoretical basis for developing high-bioavailability oral formulations of quercetin.