Land degradation is a growing concern in arid and semi-arid regions, posing severe threats to ecosystem stability, agricultural productivity, and rural livelihoods due to the combined effects of natural processes and human activities. This study examines the role of Opuntia ficus-indica (OFI), a drought-resistant cactus, in mitigating land degradation and enhancing ecosystem resilience in central Tunisia using Landsat 5 and 9 satellites with 30 m spatial resolution. Spatio-temporal dynamics of land use/land cover (LULC) and variations in key spectral indices sensitive to vegetation and soil conditions were analyzed over the period from 2000 to 2024. Using a remote sensing-based multi-index framework, Land Degradation Index (LDI) maps were generated for 2000–2010 and 2010–2024 sub-periods. Change detection analysis revealed a marked reduction in moderate-to-severe land degradation, particularly in areas characterized by OFI expansion. NDVI values associated with OFI increased significantly, from less than 0.1 in 2000 to about 0.18 in 2024, indicating enhanced vegetation vigor and improved adaptive capacity under semi-arid climatic conditions. To further assess species performance, correlation analyses were conducted between NDVI-OFI values and topographic variables, including elevation and terrain curvature. Results show a strong positive relationship between NDVI-OFI and elevation, with a clear temporal improvement from 2000 to 2024. In addition, NDVI values were highest in convex terrain forms (0.2), highlighting OFI’s ability to thrive in erosion-prone and topographically exposed environments. Findings confirm the effectiveness of OFI in reversing land degradation processes, supporting restoration through an integrated approach combining multi-temporal remote sensing and topographic analysis. The study highlights the potential of OFI as a cost-effective and scalable nature-based solution for land rehabilitation in semi-arid regions.