<p>BCS class IV drugs have poor water solubility and permeability, which provide formulation issues due to partial or unpredictable absorption patterns and low bioavailability. This study aims to formulate a ternary solid dispersion of Cefditoren Pivoxil (CFDTPI) with β-cyclodextrin (β-CD) and sugar as carriers, and explore the effect of different types of sugars and sugar alcohols on the solubility, dissolution, and bioavailability of CFDTPI. CFDTPI’s interaction with sugars and β-CD was investigated by molecular docking studies. We conducted phase solubility tests to estimate the stability constant (Ks), complexation efficiency (CE), and Gibbs free energy (ΔG°). Binary and ternary solid dispersions were prepared using the kneading method, and their saturated solubility and in vitro dissolution were evaluated. A pharmacokinetic study was also conducted to determine the bioavailability of the prepared solid dispersions when compared to the pure drug. CFDTPI had a greater and more stable binding affinity with β-CD and sugars. The ternary solid dispersion, specifically the CP: β-CD: Mannitol 0.5% (1:1:0.5%), demonstrated superior dissolution with 99.29% drug release after 75&#xa0;min, surpassing the pure drug (8.92%) and binary SD (61.63%). Solid-state research indicated that CFDTPI was trapped in the β-CD cavity, resulting in a more hydrophilic environment that improved solubility and dissolution. The pharmacokinetic study showed a 147.77% increase in bioavailability, demonstrating the effectiveness of β-CD and sugars in enhancing CFDTPI’s performance.</p>