Growing number of the sulfonamide adulteration in supplements has become a global problem due to their wide distribution and serious negative health effect. In this study, UHPLC-high resolution (HR) mass spectrometry method was developed for selective screening of 35 sulfonamides in supplements. Extraction of sulfonamides from dietary supplements was performed by simple pH control liquid-liquid extraction taking consideration into sulfonamide’s unique properties. The separation of 35 sulfonamides was effectively achieved with solid inner core of shell particles C18 column within 7 min using 10 mM ammonium acetate in water (at pH 8) and acetonitrile. From the MS/MS spectra of sulfonamides, common ions (m/z 77.9655 [SO2N]-and m/z 79.9812 [SO2NH2]-) and neutral loss fragments (HCl and SO2) were found. HR-extracted common ion chromatograms (HR-ECICs) and neutral loss scan (NLS) could enable to selectively screen the sulfonamides in various types of supplements. Also, these characteristic HR fragments based on narrow mass window within mass tolerance ±5 ppm could cover targeted as well as new emerging sulfonamide class drugs and avoid false positive or negative results in dietary supplements. Overall calibration curves within dynamic range for all targets were shown to be linear correlation coefficient R2>0.995 and limits of detection (LOD) ranged 0.04-11.18 ng/mL for all sulfonamides. The developed method will be helpful for the protection of the abuse of sulfonamide diuretics and anti-diabetics in dietary supplements, ensuring public health and consumer safety.