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Diphenhydramine (/ˌdaɪfɛnˈhaɪdrəmiːn/; abbreviated DPH, sometimes DHM) is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties that is mainly used to treat allergies. It is also used in the management of drug-induced parkinsonism and other extrapyramidal symptoms. The drug has a strong hypnotic effect and is FDA-approved as a nonprescription sleep aid, especially in the form of diphenhydramine citrate. It is produced and marketed under the trade name Benadryl by McNeil Consumer Healthcare in the U.S., Canada, and South Africa (trade names in other countries include Dimedrol, Daedalon, and Nytol). It is also available as a generic or store brand medication.

Diphenhydramine was one of the first antihistamines developed in the late 1940s and is the prototype of the ethanolamine class of first-generation antihistamines, which also includes orphenadrine, phenyltoloxamine, doxylamine, and halogenated diphenhydramine derivatives. It was first synthesized by George Rieveschl and first made publicly available through prescription in 1946.

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