The oral bioavailability (BA) of a drug is one of the key success factors for drug discovery and development. Computational BA prediction is anticipated to be a powerful tool to enable developing a high quality drug product and optimizing the therapeutic value. However, it still remains a big challenge to achieve accurate BA prediction. BA is determined by complex interactions between the physiological properties of a drug and the physiological conditions of the gastrointestinal (GI) tract. The GI environment changes dynamically with a concomitant intake of food and other drugs. Our research goal is to provide a scientific basis for BA prediction. We are experimentally investigating the physicochemical interactions between a drug and biological GI components at the molecular level. Mathematical models to describe the interactions are also investigated. We actively collaborate with pharmaceutical companies to achieve our research goal and implement the achievements in drug discovery and development.