diphenhydraminePronunciation: /ˌdʌɪfɛnˈhʌɪdrəmiːn/Definition of diphenhydramine noun [mass noun] Medicine an antihistamine compound used for the symptomatic relief of allergies. A synthetic amine, usually used as a hydrochloride salt; chemical formula: C17H21NO Origin: 1940s: from diphen- (denoting the presence of two phenyl groups) + hydr- + aminediphenhydramine in other Oxford dictionaries Definition of diphenhydramine in the US English dictionary