As one of the primary medicinal species of Glycyrrhiza under state key protection, Glycyrrhiza iflata has the characteristics of light-loving, drought-tolerant, heat-resistant, and salt-tolerant, and belongs to the dominant species in Xinjiang extreme desert ecosystem. Based on 130 effective distribution records and 8 environmental factors in China, the Maxent model was used to construct the potential geographical distribution pattern of Glycyrrhiza iflata in the last glacial maximum, middle Holocene, modern and future (2050). Essence Results show that: (1) The key climate restrictions that affect the geographical distribution of Glycyrrhiza iflata is the average annual precipitation. (2) The modern area of Glycyrrhiza iflata is 18.3 × 105km2. (3) Under the low emission scenario from the last interglacial maximum to 2050, the potential habitable area is 18.1×105km2, and the reduced area is 4.2×105km2, with a reduction rate of 19.0%. The highly suitable area was 2.5×105km2, and the reduced area was 2.8×105km2, with a reduction rate of 52.6%. (4) From the last glaciation maximum to the middle Holocene, the geographical distribution center shifted to the southwest margin of the Kumtag Desert, Xinjiang. Since then, the geographical distribution center of Glycyrrhiza iflata will continue to migrate to the southwest, but it’s going to stabilize in the future (2050). These results provided theoretical basis for the protection, utilization, origin, and evolution of Glycyrrhiza iflata.