RationaleIllegal addition of anti‐infective drugs to cosmetics at low concentrations has been found. The illicit addition of anti‐infective drugs encompasses a wide variety of medications. The current sample purification methods are inadequate to detect all these compounds. A sensitive, wide‐coverage, and weak‐matrix‐effect measurement method needs to be established to address this issue.MethodsSamples were extracted using acetonitrile, diluted 25 times, and then analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to detect 111 anti‐infective drugs. The method was validated and assessed for matrix effect before being applied to cosmetic products.ResultsThe calibration curves for the analytes exhibited a strong correlation coefficient (r > 0.995). The limit of detection ranged from 0.006 to 0.6 mg/kg. Matrix effects were significantly improved after a 25‐fold dilution. The method was successfully applied to various cosmetics. Two of 82 samples tested contained lincomycin and miconazole, respectively.ConclusionsThe developed method is quick and reliable to analyze anti‐infective drugs in cosmetics, with potential for both qualitative and quantitative analyses. It is a valuable tool for cosmetic research and development, contributing to safer and more effective cosmetic products.