In present work, chemometric-assisted UV spectrophotometric and RP-HPLC methods weredeveloped for the simultaneous estimation of caffeine (CAF) and Sodium benzoate (SB) in their combined pharmaceutical dosage form. The two chemometric methods i.e. principle component regression (PCR) and partial least square regression (PLS) were successfully applied to quantify each drug in mixture using UV absorption spectra in range of 220 – 280 nm at Δλ of 1 nm. Chemometric model development was done using 30 binary solutions and 10 solutions were used for validation of models. The chemometricmethod does not require any prior separation step. In addition RP-HPLC method was developed using HiQSil C18 column with a mobile phase consisting of methanol: acetate buffer (50:50 % v/v), pH adjusted to 4.4 with UV detection at 224 nm and flow rate of 1 ml/min. The methods were successfully applied for the simultaneous determination of these drugs in synthetic mixture.The results obtained for analysis by PCR and PLS methods were compared with RP-HPLC method and a good agreement was found.