The Greater Mekong Subregion includes five countries in the middle and lower reaches of the Mekong River (Myanma, Laos, Thailand, Cambodia, and Vietnam). In recent years, due to China's policy of fully exploiting the potential of the Mekong River's water resources upstream, as well as in other countries in the region, has led to a situation of water security in countries, especially in the Mekong Delta. The lower Mekong countries are seriously threatened. The issue of water security for the countries of the Mekong Sub-region is facing great challenges, with many potential risks that can lead to disputes and conflicts. From a regional perspective, we will clarify the current state of water security, explain some causes, and analyze the relationship between countries in the Greater Mekong Sub-region in protecting water security and especially Vietnam's role in that relationship to see the achievements that the countries have achieved, as well as the challenges posed in the coming time. At the same time, the article suggests some policies and measures that Vietnam has been, is and will be implementing in its interaction with countries in the Mekong Sub-region for the goal: of a peaceful Mekong River region Sustainable Development.