Dipyridamole (DIP) has shown promising effectiveness in treating Inflammatory Bowel Disease (IBD), especially in pediatric populations. However, existing formulations are unsuitable for children due to poor solubility and swallowing difficulties. This research aims to develop a novel DIP formulation with improved dissolution rate and bioavailability, tailored for children, using computational and experimental methods. Molecular dynamics modeling was employed to identify the optimal crystal inhibitor for DIP, with Soluplus emerging as the best candidate. This result was further validated through dissolution tests. A dry nanosuspension was then prepared using a wet milling approach followed by freeze-drying. The optimal formulation was evaluated in various dissolution media, resulting in significant improvements. Characterization techniques such as Dynamic Light Scattering (DLS), Powder X-ray Diffraction (PXRD), and Field Emission Scanning Electron Microscopy (FESEM) confirmed the crystalline state and particle size of DIP in the optimal formulation. Subsequent cell and animal studies demonstrated that the optimal formulation outperformed both the commercial product and pure DIP. The absolute bioavailability of pure DIP, commercial tablets, and optimal formulation was 9.51%, 18.17%, and 42.15%, respectively. Physiologically based pharmacokinetic (PBPK) modeling was then utilized to predict and evaluate the in vivo behavior for both adult and pediatric populations, showing good performance in both groups. In conclusion, our study successfully developed a DIP dry nanosuspension with improved dissolution and bioavailability, specifically tailored for pediatric use. The combination of computational and experimental methods offers a strong foundation for future formulation development, significantly reducing both time and costs.