Increase popularity of polyphenol's use in a wide range of health benefit including diseases prevention and therapeutic agent in addition to considering that diet-derived compounds and herbal medicine are generally regarded as safe, it is becoming increasingly apparent that these compounds could have deleterious effects and could raises concerns about the safe use of dietary flavonoids. The risk of polyphenols-trace elements or drugs pharmacokinetic interaction poses two major extremity challenges, pharmacotoxicity and treatment failure. this work was done to clarify the importance of such subject and to explain that supraphysiological or pharmacological doses of polyphenols have different effects