Burkina Faso’s protected areas are under pressure from human activities, in particular agricultural expansion. In addition to the effects of climate change which are a major cause of land cover modifications. Together, these factors causes the loss of biodiversity in protected areas. The main objective of this study is to analyze changes in the spatial structure of the Deux Balé National Park, Burkina Faso. Land cover maps of the park for the years 1986 and 2016 were used for the calculation of the landscape indices and the transition matrix approach allowed to better quantifying the changes in the landscape of the park. The results reveal three processes of change, including i) the fragmentation of tree savannahs, ii) the creation of new shrub savannahs patches, anthropogenic zones, bare soils and water bodies and iii) the removal of gallery forests. The processes of fragmentation and suppression of classes comprising tree cover are mainly related to human activities. This is a danger to the conservation of biodiversity in this park if no corrective measures are taken to reverse the trend.