The Mekong Delta, a vital agricultural and ecological region in Vietnam, experiences serious challenges from flooding, saltwater intrusion, and freshwater shortages. These issues, worsened by climate change and upstream developments, are endangering the region's sustainable development and are causing great concern for the local population and authorities. This study examines traditional strategies for addressing challenges to freshwater availability, tidal flooding, and saltwater intrusion in this area. The disadvantages of different strategies are highlighted, and a novel approach involving the construction of large multi-functional barriers in the main estuaries of the Mekong Delta is presented. The idea has been preliminarily considered for the Ham Luong estuary region in Ben Tre province, which is among the most vulnerable to the abovementioned threats. The large barrier at the main estuaries can be integrated with river and sea dikes to form new coastal reservoirs, offer flexible operational capabilities to manage saltwater intrusion, and protect the landside from tidal inundation as well as storm surges. Moreover, a schematized model of the Ham Luong estuary was developed using Delft3D to assess the hydrodynamic impact of the proposed barriers. The numerical results indicate that strategically positioning the opening and closing gates in alignment with flood and ebb flow patterns and increasing the structure's opening can considerably mitigate the adverse effects of the estuarine barriers. This research highlights the potential of an innovative multi-functional flood defense system at the main entrance of the estuary to ensure water security and support sustainable development in the Mekong Delta.