In this study, core–shell magnetic molecularly imprinted polymer nanoparticles (MMIP-NPs) were synthesized and then used for the extraction of chlordiazepoxide (CLD) from various samples prior to its determination by high-performance liquid chromatography (HPLC). First, Fe₃O₄ nanoparticles were prepared using a coprecipitation method, stabilized with tetraethyl orthosilicate (TEOS) and functionalized with 3-(trimethoxysilyl)propyl methacrylate (MPS). Then, MMIPs were synthesized under distillation conditions through the precipitation polymerization using methacrylic acid (MAA) as a functional monomer, CLD as a template, ethylene glycol dimethacrylate (EGDMA) as a cross-linking agent and azobisisobutyronitrile (AIBN) as an initiator. The properties of the MMIPs were characterized using Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The effective variables on the extraction recovery (ER) such as the amount of MMIP, time of adsorption, pH and volume of the desorption solvent were optimized by central composite design (CCD) combined with desirability function (DF). The extraction conditions were optimized and the values of variables were set as 11 mg of adsorbent, 10 min adsorption time, pH = 5.5 and 1.4 mL of methanol. The linear response (r² > 0.998) was obtained in the range of 0.006–10 μg mL⁻¹ with a detection limit 0.0014 μg mL⁻¹ and the ER was in the range of 90–96% with a relative standard deviation (RSD) of <5.0% (n = 3).