Dietary supplements used for improving brain function and strengthening attention are increasingly popular. However, illegal dietary supplements containing unapproved drugs continue to be seized. Therefore, it is necessary to rapidly screen and identify adulterated compounds in dietary supplements for public safety. To develop the simultaneous analytical method, we selected 11 nootropic compounds and optimized the simultaneous liquid chromatography‐electrospray ionization‐tandem mass spectrometry and optimal conditions for liquid chromatography‐quadrupole time‐of‐flight mass spectrometry were proposed to determine the fragmentation patterns of each compound. The specificity, linearity, limit of detection, limit of quantification, method detection limit, method quantitation limit, precision, accuracy, matrix effect, and stability of this method were evaluated according to international validation guidelines. The validated methods were applied to 54 samples containing dietary supplements and seized samples. On screening 11 nootropic compounds were detected in four solid samples (tablet and powder). By comparing the product ion ratios with the standards and quantification, vinpocetine (6.52–34.2 mg/g) was found in three samples, and omberacetam (995.6 mg/g) in one sample. To re‐confirm the detected compounds, the fragmentation patterns were compared with those of the standards using liquid chromatography‐quadrupole time‐of‐flight mass spectrometry. The developed simultaneous analysis method can help maintain public health and safety.