The lethal dose of diphenhydramine, the generic name of Benadryl, varies significantly from person to person because of differences in weight and metabolism. There have been cases of people experiencing overdose symptoms with 500 milligrams of diphenhydramine and some cases where overdose is as high as 2,800 milligrams.
The drug has a high therapeutic index, meaning that the dose needed to cause death is many times higher than that needed to produce beneficial effects. It is not recommended to use more than 300 milligrams daily, according to MedicineNet. That amount is to be divided among several 25- to 50-milligram doses taken every four to six hours. It is never recommended to take more diphenhydramine than is necessary to alleviate the symptoms it is used to treat.