A novel magnetic organic polymer FeO@SiO@Tb-PDAN was designed and synthesized, which was used as an adsorbent for magnetic solid-phase extraction (MSPE) of 16 macrolides (MALs) in water and honey. The synthesized adsorbent was characterized using techniques including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Then several parameters of the extraction process were further optimized. Under the optimized conditions, an MSPE-LC-MS/MS method was established for extraction and determination of 16 MALs, which showed good linearity ( ≥ 0.999), low limits of detection (0.001-0.012 μg L for water and 0.001-0.367 μg kg for honey) and satisfactory recoveries (70.02-118.91%) with the relative standard deviations (RSDs) lower than 10.0%. This established method was then successfully applied to detect MALs in real samples, which suggested that FeO@SiO@Tb-PDAN was a potential magnetic adsorbent for efficient extraction and analysis of MALs.