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The 2303 Wetlands of International Importance distribute unevenly in different continents. Europe owns the largest number of sites, while Africa has the largest area of sites. More than half of the sites are affected by three or four impact factors (55%). The most significant impact factors are pollution (54%), biological resources use (53%), natural system modification (53%), and agriculture and aquaculture (42%). The main affected objects are land area and environment of the wetlands, occurred in 75% and 69% of the sites, respectively. The types most affected by land area occupation are river wetlands and lake wetlands, the types with the greatest impact on environment are marine/coastal wetlands and river wetlands, the type with the greatest impact on biodiversity is river wetlands, the types most affected by water resources regulation are marsh wetlands and river wetlands, and the types most affected by climate change are lake wetlands and marine/coastal wetlands. About one-third of the wetland sites have been artificially reconstructed. However, it is found that the proportions of natural wetland sites not affected or affected by only one factor are generally higher than that of wetland sites both containing natural wetlands and human-made wetlands, while the proportions of wetland sites both containing natural wetlands and human-made wetlands affected by three or four factors are generally higher than that of natural wetland sites. Wetland sites in the UK and Ireland are least affected among all countries. Wetland management plans in different regions still have large space for improvement, especially in Africa and Asia. The protection and restoration of global wetlands can be carried out in five aspects, including management and policy, monitoring, restoration, knowledge, and funding.