A simple and reliable UV spectrophotometric and high-performance liquid chromatographic (HPLC) methods were developed and validated for simultaneous determination of moexipril hydrochloride (MOE) and hydrochlorothiazide (HCT) in pure form and pharmaceutical dosage forms and biological fluids (serum and urine). The first method was a RP-HPLC method which was performed using ACE Generix 5 C18 column (5 μm practical size, 25 cm x 4.6 mm i.d.). The flow rate, the injection volume and the detection wavelength were 1.0 mL min-1, 20 μL and 200 nm, respectively. The mobile phase consisted of 0.05 mol L-1 pentane sulfonic acid sodium salt at pH 3 and acetonitrile (50:50, v/v). The retention times for MOE and HCT drugs were found to be 4.21 ± 0.15 min and 2.98 ± 0.07 min, respectively. The second method was ratio spectra derivative (1DD) spectrophotometric method. Calibration curve was linear over the concentration range of 0.1-150 μg mL-1 and 0.1-300 μg mL-1 using RP-HPLC method and 2.0-11.0 μg mL-1 and 1.0-12.0 μg mL-1 using UV method for MOE and HCT drugs, respectively. The analytical validation and recovery study were performed to confirm the accuracy of the proposed methods. The methods were validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The developed RP-HPLC and UV spectrophotometric methods were successfully applied for the simultaneous determination of moexipril hydrochloride and hydrochlorothiazide drugs in pharmaceutical dosage forms and biological fluids (serum and urine).