<p>Reversed phase HPLC method and normal phase HPTLC method have been optimized, validated and compared for simultaneous assessment of Bilastine (BLN) and Montelukast sodium (MLS) in commercial tablet formulation. As per a review of the literature, no articles have reported on a comparison of HPLC and HPTLC methods for a simultaneous determination of BLN and MLS in a pharmaceutical dosage form. The objective of this study is to develop easy and cost-effective analytical methods for simultaneous quantification of BLN and MLS. A C18 column (25 cm × 0.46 cm, 5 μ) as a stationary phase and methanol:0.5% orthophosphoric acid (80:20, v/v) as an eluent with a flow rate of 1.0 mL/min were used for HPLC separation, while a stationary phase, readymade silica gel G60F₂₅₄ plate and mobile phase, Chloroform:Benzene:Methanol:Ammonia (3:5:2:0.2, v/v/v/v) with chamber equilibrium time of 40 min were used for HPTLC separation. Validation of both methods was performed according to ICH quality guidelines (Q2R1). BLN and MLS were eluted at 3.303 min and 5.570 min, respectively, and the retardation factor was observed, respectively, to be 0.29 and 0.45. Both methods passed validation parameters and were used for the assessment of BLN and MLS in commercial tablets. The given HPLC and HPTLC methods were simple, sensitive, accurate, robust and can be applied for regular quality analysis of dosage forms containing BLN and MLS.</p>