Due to its biodiversity, ecosystem services offered, and deforestation experienced since the 16th century, there are several protected areas in Atlantic Forest, such as the Juréia-Itatins Protected Areas Mosaic (JIPAM), state of São Paulo, Brazil. Illegal deforestation in the JIPAM and surroundings have been increasing, caused by urban and agricultural expansion. Landscape naturalness scenarios of JIPAM and surroundings for 2050 year were simulated, considering the periods 1985–2002 and 2002–2019, which correspond, respectively, to the scenarios before and after the creation of the JIPAM and National System of Protected Areas (NSPA). The landscape naturalness was evaluated by generating Distance to Nature index (D2N) maps for years 1985, 2002 and 2019, which was used as input data in simulation. The forecasting of both scenarios was conducted using cellular automata, weights of evidence and Markov chain, in Dinamica EGO platform. Both projections indicated that there would be a slight decrease in landscape naturalness. However, the scenario with JIPAM and NSPA can be considered the most effective in guiding the study area toward a conservation profile, as it would contribute to a reduction of approximately 32% of non-natural areas located within mosaic, in relation to another scenario. The NSPA and the creation of the JIPAM have contributed to maintain the study area naturalness, reducing losses in landscape naturalness. Nevertheless, municipal planning and the JIPAM management plans should consider urban and agricultural expansion and access roads as important drivers of loss of landscape naturalness, triggering deforestation and biodiversity damages.