The aim of the study was to develop an amorphous solid dispersion of a poorly water-soluble drug with high melting point by ball milling and hot melt extrusion as a co-processing method. Solid dispersion systems were prepared by ball milling-hot melt extrusion and then compared with those prepared with hot melt extrusion. The effects of three process parameters in the co-processing method, namely, barrel temperature, screw speed, and cooling rate, were systematically studied. The physical state of prepared solid dispersion was characterized by differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, phase solubility, and dissolution study.The Resveratrol-Eudragit® EPO system exhibited good miscibility and significant dissolution enhancement. Resveratrol in the amorphous solid dispersion existed in an amorphous state and had molecular interactions with Eudragit® EPO. Stability studies showed no apparent difference in the physical state of the solid dispersion after 6 months. In conclusion, combining ball milling with hot melt extrusion is a promising method for preparing the amorphous solid dispersion of a poorly water-soluble drug with high melting point. Fig. 6 The dissolution curves of RES from solid dispersions under different parameters: (a) ball milling time, (b) ball milling frequency, (c) barrel temperature, (d) screw speed, (e) cooling rate.