Habitat degradation and climate change are major threats to the long-term persistence of reptile populations. However, their roles on primary productivity instability remain unclear at certain scales. Besides, the design of protected areas has often overlooked reptiles or assumed that their ecological requirements are represented under the umbrella of more charismatic species. Here, we assess the vulnerability of areas of high diversity of reptiles in the Iberian Peninsula to global change using data from satellite imagery. We focused on primary productivity, climate and land-use change because they are indicators of environmental variability that might impair ecosystem functioning and alter wildlife communities. We used linear regressions to detect monotonic temporal trends in primary productivity (through the enhanced vegetation index, EVI) and climate (mean temperature and accumulated precipitation) at two spatial resolutions (10-km2 UTM squares and CORINE land-cover polygon level) over the period 2000–2020. We also determined how the strength of land-use and climate change affected the intensity of change in primary productivity at both spatial scales with multivariate linear regressions. We identified 339 hotspots (10-km2 UTM squares) and monotonic increments of temperature, EVI or both occurred in 43 %, 16 % and 22 % of them, respectively. Positive trends of the EVI were related to increasing temperatures and changes in shrubland and forest cover. Within the hotspots with monotonic increments in EVI and temperature, EVI increments occurred in 65 % of the CORINE polygons that did not change their land-cover type, with stronger increases in tree crops. Finally, the Natura 2000 network provides only moderate protection to reptile hotspots, being most of the vegetation types relatively underrepresented. The proportion of forest and shrubland protected by the Natura 2000 network was higher in hotspots where EVI changed. Our procedures are relevant to prioritize hotspots requiring ground monitoring that allows economic and time savings.