Ketoprofen (KTP), an active pharmaceutical ingredient with poor solubility in water and other aqueous solvents, has gained attention for its improved solubility and quicker therapeutic effects when combined with cyclodextrin (CD). This study thoroughly examines how varying concentrations of CD affect KTP, leading to notable increases in absorbance and fluorescence intensity. The binding constant for the 1:1 complex is determined from these changes. Ultrasonication enabled the successful formation of inclusion complexes (ICs) of KTP with β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HβCD), referred to as KTP:βCD IC and KTP:HβCD IC, respectively. Significant differences in chemical shift values and surface morphology are observed for the ICs compared to their uncomplexed form. The thermal stability of KTP is markedly improved when combined with CDs. The HOMO-LUMO relationship stabilizes the complex through favorable interactions and electron transfer action within the ICs. Additionally, protein denaturation assays showed significant enhancements in the anti-inflammatory and anti-arthritic activities of KTP in its IC form compared to KTP alone. Thus, due to their enhanced solubility and complexation properties, the ICs of KTP show promising potential as drug materials for solid dosage forms.