A rapid and validated stability indicating RP-HPLC method using isocratic elution and coupled with photodiode array detection was developed for quantifying the content of simethicone, domperidone, magaldrate and sodium alginate in bulk and syrup formulation. The best mobile phase used in this study consisted of 0.1 % orthophosphoric acid/acetonitrile (50/50, V/V) with a flow rate of 0.7 mL min-1. Under optimized conditions used in this study, selected drugs were eluted at 3.301 min (simethicone), 4.293 min (domperidone), 5.220 min (magaldrate) and 6.149 min (sodium alginate) within 12 min run time without any interfering excipients. Peak areas and selected drug content demonstrated excellent linearity (simethicone – 5 to 30 µg mL-1; domiperidone – 2.5 to 15 µg mL-1; magaldrate – 120 to 720 µg mL-1; sodium alginate – 25 to 150 µg mL-1). Percent recovery, which represents accuracy, was 99.12–100.18 % for simethicone, 99.59-100.52 % for domperidone, 99.23-100.25 % for magaldrate and 99.57-100.02 % for sodium alginate. Percent relative standard deviation, which represents precision, was observed in the range of 0.078-0.983 % (simethicone), 0.528-0.861 % (domperidone), 0.278-1.069 % (magaldrate), 0.316-0.572 % (sodium alginate). The developed method displayed favourable accuracy and recovery and was suitable for determining the content of simethicone, domperidone, magaldrate and sodium alginate combination in syrup formulations.