The invention provides a high temperature-resistant heat-sealing adhesive for a high-speed medicine packaging machine for medicine blister packaging. The high temperature-resistant heat-sealing adhesive comprises, by mass, 20-39.9% of modified polyolefin resin, 10-20% of modified epoxy resin, 50-60% of a solvent and 0.1-0.5% of an assistant. A preparation method of the high temperature-resistant heat-sealing adhesive comprises the following steps: S1, adding the solvent into a reaction kettle, performing stirring to achieve uniform mixing, sequentially adding the modified polyolefin resin andthe modified epoxy resin while stirring, and stirring and uniformly mixing the solvent, the modified polyolefin resin and the modified epoxy resin; S2, adding the assistant to a mixed solution obtained in step S1, performing high-speed stirring to achieve uniform mixing, and performing downtime curing; and S3, measuring the solid content, adjusting the solid content to a theoretical value, and performing stirring, cooling and filtering. Compared with heat-sealing adhesives in the prior art, the heat-sealing adhesive in the invention has the following advantages: no leakage sealing, no scorching crease marks and no peculiar smell are achieved during high-temperature and high-speed sealing using the medicine packaging machine; the heat-sealing strength is high, so product demands are met; anadhesive layer has a good stability, and the strength of a coating film does not change after the coating film is stored for one year; and the heat-sealing adhesive has a wide application range.