Tea beverages such as green, oolong and black teas are very popular in the world. Recently, green tea extract-based dietary supplements including a large amount of green tea polyphenol (GTP) have been widely consumed to expect beneficial health as anti-aging, weight reduction and etc. Although tea beverages are considered to be innocuous, the large ingestion of GTP from dietary supplements and the administration of a drug with GTP often produce some serious effects. The GTP with high physiological activity can interact with some drugs to affect the absorption, bioavailability and efficacy of the drug. Therefore, it is very important on medicinal treatment to analyze the compatibility and the mechanism for drug interaction with GTP using isothermal titration microcalorimetry (ITC) and molecular modeling calculation (MMC). It is concluded that ITC is the most suitable and powerful measurement method to analyze interaction between drugs and bioactive substances in tea beverage, supplement and health food. ITC can bring some useful information in medical treatment and elucidate the drug interaction at the molecular level by combination with MMC.