The invention provides a kit for detecting anti-depressant drugs in serum and plasma by liquid chromatography tandem mass spectrometry. The kit comprises drug standard substances, drug internal standardization compounds, drug extraction compositions, negative plasma and a diluent. The drug standard substances comprise amfebutamone, oxybupropion, citalopram, Escitalopram, venlafaxine, O-desmethylvenlafaxine, duloxetine, fluoxetine, norfloxetine, fluvoxamine, mirtazapine, paroxetine, sertraline and trazodone. The drug internal standardization compounds comprise amfebutamone-d9, oxybupropion-d6,citalopram-d6, venlafaxine-d6, O-desmethylvenlafaxine-d6, duloxetine-d3, fluoxetine-d6, norfloxetine-d6, fluvoxamine-d4, mirtazapine-d3, paroxetine-d6, sertraline-d3 and trazodone-d6. The drug extraction compositions comprise, by volume, 60% of methanol solution, 20% of acetonitrile solution, 10% of isopropyl alcohol solution and 10% of purified water. The diluent comprises 50 % of methanol waterfluid. The kit can be used for simultaneous detection of the anti-depressant drugs and active metabolites, the detection time is short, and flux is high.