•Computational simulation of 3D structures of two molecules and four phenothiazines.•Synthesis of two dummy templates based molecularly imprinted polymers (MIP).•Develop a MIP-SPE column for determination of phenothiazines residues in meats. The 3D structures of two dummy templates and four phenothiazine drugs were studied by using computational simulation method. Then the two dummy templates were used to synthesize two molecularly imprinted polymers respectively. Results showed that the recognition abilities of the two polymers were consistent with the theoretical calculation. Then a solid phase extraction column was developed for extraction of the four phenothiazines in meat (pork, chicken) followed by determination with high performance liquid chromatography. The column showed high adsorption capacities (850–962ng analyte per milligram of polymer) and high recoveries (93–98%) to the four drugs, and could be recycled for sixty times. The limits of detection were in the range of 1.0–10ng/g, and the recoveries from the fortified blank samples were in the range of 70.3–96.1%. This is the first study reporting the use of molecularly imprinted polymer-based method for determination of phenothiazines residues in foods.