An experimental design (ED) approach was applied to study the weight of three factors in the synthesis of a molecularly imprinted polymer (MIP) specific for iprodione fungicide. The objective was to obtain a high specific polymer with the best performance of iprodione binding. Thirteen iprodione-imprinted polymers and 13 non-imprinted polymers (NIP) were synthesized according to ED having 3 influencing factors: the polymerization method, the crosslinker nature and the functional monomer type. For each factor, two levels were studied: bulk and precipitation polymerization for the first factor, trimethylolpropane trimethacrylate (TRIM) and ethylene glycol dimethacrylate (EGDMA) for the second factor, and methacrylamide (MAM) alone or with styrene for the third factor. The ED responses were: the imprinting factor, the site number and the apparent affinity constant. They were determined after studying the interactions between iprodione and each MIP and NIP in hydro-alcoholic medium. The best polymer of the ED was synthesized using MAM as functional monomer, EGDMA as crosslinker and precipitation polymerization. It has an imprinting factor of 2.4, a site number of 1172 and an affinity constant of 19.36. The best MIP was characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Nitrogen sorption isotherms. The best MIP has a mesoporous structure with a high specific surface area of 407 m2·g− 1. Molecularly imprinted solid phase extraction (MISPE) was successfully applied, using the best MIP, to preconcentrate iprodione from a white wine containing two competing fungicides.