Objective To comprehensively compare and screen glycoprotein preparation processes for six representative medicinal materials from the genus Panax.Methods Glycoprotein yield, DPPH radical scavenging capacity, hydroxyl radical scavenging capacity, and Fe²⁺ chelation inhibition rate were used as evaluation indicators. Glycoprotein extraction rates and antioxidant activities of six medicinal materials, including P. ginseng, P. notoginseng, P. quinquefolius, P. japonicus (T.Nees) C.A.Mey., P. stipuleanatus H.T. Tsai K.M. Feng, and P. bipinnatifidus Seem, were compared using traditional thermal extraction and ultra-high pressure processing (UHPP). The Box-Behnken response surface method was employed to optimize UHPP parameters for P. quinquefolius glycoproteins with the highest antioxidant activity.Results UHPP produced higher glycoprotein extraction rates for all six Panax species compared with thermal reflux extraction. P. quinquefolius glycoproteins exhibited significantly higher DPPH radical scavenging capacity, hydroxyl radical scavenging capacity, and Fe²⁺ chelation inhibition rate than the other species, demonstrating the strongest antioxidant activity among UHPP-extracted glycoproteins. The optimal UHPP conditions for P. quinquefolius glycoprotein extraction were as follows: extraction time of 12 min, extraction pressure of 400 MPa, and solid-to-liquid ratio of 1∶18 (g/mL). Under these conditions, the glycoprotein content reached 25.27%, deviating only 0.14% from the predicted value, representing a significant improvement over traditional reflux extraction.Conclusion UHPP technology can be used to prepare glycoproteins from Panax species with high antioxidant activity.