Ephedra equisetina as a national secondary protected plant has great medicinal and economic value. It also plays an important role in preventing water and soil erosion, keeping ecological balance, desertification governance and other aspects. However, the deterioration of the global climate as well as human activities seriously threatens the conservation and utilization of E. equisetina resources. Therefore, it is of great significance to predict the changes in the potential suitable areas of E. equisetina. Based on MaxEnt model and ArcGIS software, we combined 201 effective distribution records of E. equisetina in China and 21 environmental variables selected, this study predicted the changes of potential suitable areas of Chinese herbal medicines E. equisetina under two scenarios of natural environmental disturbance and human activity disturbance in the future. In addition, the predicted highly suitable areas of E. equisetina and land use types were superimposed by analysis. The results showed that: (1) After adding the human activity factor to the MaxEnt model, the area under curve (AUC) increased from 0.919 to 0.948, and the accuracy of the prediction results was improved. However, we noticed that the area of the totally suitable areas of E. equisetina under the disturbance of human activities was seriously reduced, and some of the suitable levels had degraded, with the distribution of suitable areas became more sparse, scattered and fragmented. (2) The suitable areas of E. equisetina were mostly distributed in Gansu, Ningxia, Shaanxi, Shanxi, and Xinjiang. Both scenarios for the future period showed different degrees of expansion in the suitable areas of E. equisetina. Compared with the current period, the representative concentration pathways of 2.6 for the period of 2050 (RCP2.6-2050), which has the largest increase in the highly suitable areas of E. equisetina. (3) Acidity and basicity (pH), altitude (Altitude) and annual mean temperature (Bio1), which were the higher contributors among the 21 environmental factors involved in the modeling, and these three factors had a significant influence on the geographical distribution of E. equisetina. (4) The geometric centroid of the highly suitable areas was projected to move eastward, distributed mostly in Gansu Province. (5) Some parts of the land in the potentially highly suitable areas of E. equisetina had already been developed and utilized, and the remaining little unused land was distributed in Xinjiang, Gansu, Inner Mongolia and Ningxia, where could be suitable for the development of E. equisetina cultivation industry according to local conditions. All of these provide the theoretical basis for in-situ conservation, ex-situ conservation, priority protection areas and site selection for artificial cultivation of E. equisetina, which is of great practical significance for the protection and sustainable utilization of E. equisetina resources.