The temporal and spatial dynamics of biodiversity and its future trends are of great significance for maintaining biodiversity pattern and ensuring regional ecological security in the Nanliu River Basin of Beibu Gulf. At present, most studies are concerned with the assessment of biodiversity in historical period, but few studies focused on the prediction of biodiversity under several scenarios in future years, and the history and future spatial simulation of habitat quality has not been carried out. Therefore, the establishment of biodiversity simulation studies under different scenarios in the future plays a crucial role in the sustainable development of regional social economy. This study takes Nanliu River Basin, which only flows into the sea in the Beibu Gulf, as the research object. Based on land use data and social and economic data interpreted from remote sensing data in 2000, 2010 and 2020, Conversion of Land Use and its Effects at Small Region Extent (CLUE-S) model was used to simulate and predict land use patterns for ecological protection scenarios, natural growth scenarios and food security scenarios in 2030. The Integrated Valuation of Ecosystem Service and Tradeoff (InVEST) model was used to evaluate the biodiversity of different scenarios in the past and future and discuss the habitat quality and degradation degree of biodiversity in the watershed. Results were presented as follows. In 2000–2020, an increasing trend of construction land, shrub land and water area was found in the Nanliu River basin of Beibu Gulf. The largest increase was observed in construction land, and the largest decrease was noted in cultivated land and woodland. The best habitat quality will be under the ecological protection scenario in 2030. The biodiversity in the upstream and downstream of the three scenarios showed varying degrees of improvement, and the midstream exhibited a degradation trend. The research results of this paper can make up for the vacancy of biodiversity habitat evaluation system in Nanliu River Basin at home and abroad, and have important theoretical and practical significance for promoting ecological protection and ecological planning of watershed.