The rivers and their floodplains are integrated systems. The biodiversity of the Lower Danube River (LDR), in terms of species and habitats, is strongly linked with its hydro-geomorphic-diversity and the natural regions it passes. Human activities, directly and indirectly, are the primary cause which has induced changes in hydrologic regime, longitudinal and lateral connectivity, floodplain geomorphology and function, biodiversity of the river waters and riparian zone. During the twentieth century, particularly after World War II, the LDR has undergone alteration of physical habitat, significant landscape changes, and ecological loss as a result of hydropower damming works and their associated water reservoirs, floodplain embankment, wetlands drainage, chemical pollution, eutrophication, and invasion of exotic species. The extensive embankments and drainage work along LDR in Romania converted about 80% of the annual flooded zone of the floodplain area primarily into agricultural region, obviating its essential connection with the river. Few areas, including reed marshes, meadows, floodplain forests, large shallow lakes, fluvial islands, and the braided section of the river named “the Small Island of Brăila”, have been preserved in natural regime in order to preserve valuable samples of biodiversity, hydro-morpho dynamic processes, and particular fluvial landforms. Most of them are ecotonal areas that have an increased and extremely dynamic biodiversity. This increased turnover of species is exacerbated by anthropogenic factors, which sometimes they can negatively influence certain species of fauna, such as sturgeons, modifying their habitats for reproduction, feeding and resting. After the 1990s, due to the change of the political system in Romania and following integrated programs of the Danube Riparian States, some areas of the engineered floodplain are subject to ecological restoration and integrated management in order to provide convenient ways of reconciliation between nature and human society for a sustainable development. The currently Ramsar and Natura 2000 sites network designed along the LDR provides the national and international legal framework of protection and conservation of wildlife and its habitats. The objectives of this chapter are to present a review of: (1) human interventions from the last century that lead to alteration, degradation, and irreversible losses of habitats along the LDR valley, (2) restoration projects of former floodplain areas, and (3) biodiversity protection and conservation actions carried out over the area in the last decades.