The work aims to establish an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to screen 12 common antioxidants in oral liquid medicinal composite films. With n-hexane as the extraction solvent, the target compounds were extracted through a 2-hour reflux process. The content of the target compounds was then analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Shim-pack GIST C18 (100 mm×2.1 mm, 2 μm) was employed as the chromatographic column and methanol and water were used as the mobile phase. Electrospray ionization (ESI) was utilized as the ion source, and multiple reaction monitoring (MRM) in positive ion mode was applied for qualitative and quantitative analysis. The 12 antioxidants exhibited good linearity within the concentration range of 2 to 500 ng/mL, with a correlation coefficient (r) ≥ 0.998 6. The detection limits ranged from 0.2 to 10.6 ng/g, and the recovery rates were between 78.9% and 112.7%. The relative standard deviation (RSD) ranged from 0.8% to 7.0% (n=3). Upon analysis, antioxidants were detected in all 12 batches of oral liquid medicinal composite films, with higher concentrations found in samples 1010, 1076, and 168. This method is highly efficient, sensitive, accurate, and reliable, making it suitable for the screening of 12 common antioxidants in oral liquid medicinal composite films.