Abstract: Objective: To optimize the extraction process of total alkaloids from Suaeda salsa L. and study the antioxidant activity of total alkaloids from Suaeda salsa on high-fat diet in mice. Methods: The yield of total alkaloids from Suaeda salsa was used as the index, and the orthogonal analysis was carried out on the basis of single factor experiment. The total alkaloids of Suaeda salsa were gavaged to high-fat diet mice, and the aging indexes of mice were monitored regularly. Results: The optimum extraction conditions were as follows: Ultrasonic time 20 min, ultrasonic temperature 45 ℃, ethanol concentration 85%, solid-liquid ratio 1:10. Under these conditions, the yield of total alkaloids was (0.65 ± 0.02) mg/g. The antioxidant activity test showed that the low, medium and high dose groups of Suaeda salsa total alkaloids could significantly reduce the content of MDA in the liver of mice (P<0.05), and the low(2 mg/kg), medium(4 mg/kg) and high dose(8 mg/kg) groups of total alkaloids of Suaeda salsa could also significantly increase cat and GSH-Px in liver (P<0.05). Conclusion:The optimized process has good feasibility. Suaeda salsa alkaloids can be used as the basis for the study of the total antioxidant activity of Suaeda salsa.