•A vortex-forced matrix solid phase dispersion method was established and developed.•The chistosan solution was applied as elution reagent.•The Celite AZO was employed as dispersant.•Simultaneous determination of four compounds from Ligustri Lucidi Fructus. A simple and efficient sample preparation method to extract four bioactive compounds (echinacoside, specnuezhenide, oleuropein and nuezhenoside G13) from Ligustri Lucidi Fructus was established by vortex-forced matrix solid phase dispersion (VFMSPD) method. Chitosan solution was applied as green eluent in this procedure and Celite AZO was employed as dispersant. High performance liquid chromatography (HPLC) equipped with ultraviolet (UV) detector was used to analyze the target analytes. The best result of the investigation was obtained with Celite AZO as dispersant, sample/ dispersant ratio as 1:1, grinding for 2 min, 1 mL high-viscosity chitosan solution (0.5 mg mL−1) used as the elution reagent and vortex mixing for 1.5 min. The method exhibit a good linearity for the analytes (r2 > 0.999). The absolute recoveries of the four target compounds in Ligustri Lucidi Fructus ranged from 90.7% to 98.8% and the relative recoveries of the target compounds ranged from 99.2% to 102% (RSD ≤ 3.4%), which were obtained by the final optimization method. Consequently, the newly developed chitosan solution-based vortex-forced matrix solid phase dispersion (MSPD) combined with HPLC could be efficiently applied to extract and analyze the target compounds in Ligustri Lucidi Fructus samples.