Obesity is a chronic disease associated with serious health problem such as metabolic syndrome, diabetes, hypertension, and cardiovascular disease. Recently, anti-obesity drugs, designer analogues and natural weight-loss ingredients have been found in dietary supplements for rapid weight loss or maintenance. In addition, structurally modified designer analogues are being continuously synthesized to avoid governmental inspections. 25 illegal compounds were assayed using a liquid chromatography coupled with photodiode array detector (LC-PDA) and tandem mass spectrometry (UPLC-MS/MS) analyses. A simultaneous determination method was established and fully validated. In 76 of 370 samples, nine different adulterants were detected including yohimbine, followed by β-phenylethylamine (β-PEA), sibutramine, sennoside A and B, β-methyl phenylethylamine (BMPEA), fluoxetine, ephedrine, phenolphthalein, and icariin. And 12 adulterated products contained a mixture of two or more adulterants. Adequate use of the existing regulation and the development of alternative methods for detecting adulterants are necessary consumers from consuming dietary supplements adulterated with illegal compounds.