Two simple and sensitive spectrophotometric techniques have been proposed for the estimation of antihistamine drugs, diphenhydramine hydrochloride (DPH), fexofenadine hydrochloride (FXO) and cetirizine dihydrochloride (CTZ) in pure forms and in their pharmaceutical forms via charge-transfer complex formation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) reagents. Spectrophotometric methods involve the addition a known excess of DDQ or TCNQ reagents to DPH, FXO and CTZ drugs in acetonitrile, followed by the measurement of the absorbance of formed CT complexes at the selected wavelength. Various variables and parameters affecting the reactions were studied and investigated. Beer's law was obeyed in the concentration ranges of 16-144, 12-120, 12-86 μg mL −1 and 6-66, 24-216 and 4-68 μg mL −1 for DPH, FXO and CTZ drugs using DDQ and TCNQ reagents, respectively, with correlation coefficients not less than 0.9944. The reaction stoichiometry is found to be 1:1 [drug]: [DDQ or TCNQ]. For the spectrophotometric methods, molar absorptivity, detection and quantification limits, and sandell resistance are also calculated. According to ICH guidelines, both intra-and inter-day precision and reliability were evaluated. The estimated techniques have been successfully applied in their medicinal forms to the determination of the cited drugs. The finding showed no significant difference between the estimated methods and reported methods, depended on t test and variance ratio. Popular pharmaceutical additives did not interfere.