Two simple, economical, rapid, precise, and accurate methods for simultaneous determination of olmesartan medoxomil and hydrochlorothiazide in combined tablet dosage form have been developed. The first method is based on ratio spectra derivative spectrophotometry, and the second method is zero-crossing difference spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231.0 and 271.0 nm were selected to determine olmesartan medoxomil and hydrochlorothiazide, respectively. Measurements of absorbance were carried out at zero-crossing wavelengths 257.8 and 240.2 nm for olmesartan medoxomil and hydrochlorothiazide by zero-crossing difference spectrophotometric method. Beer’s law is obeyed in the concentration range of 08–24 µg/mL for olmesartan medoxomil (OLM) and 05–15 µg/mL for hydrochlorothiazide (HCT) by ratio spectra derivative and 05–30 µg/mL for OLM and HCT by zero-crossing difference spectrophotometric method. The results of the assay were found to be 100.46 ± 0.95 for OLM and 100.4 ± 0.27 for HCT by ratio spectra derivative and 99.06 ± 1.14 for OLM and 100.05 ± 0.90 for HCT by zero-crossing difference spectrophotometric method. These methods passes F test and t test. Both methods were validated statistically and by performing recovery study.