This is a systematic review of scientific articles reporting the biodiversity of endophytic fungi isolated from endemic Cerrado plants in Brazil and exposes the potential applications of these microorganisms in the production of known and new metabolites. The “Portal de Periódicos” (CAPES), Science Direct, PubMed, Scielo, and Biblioteca Virtual em Saúde (BVS) databases were used. A total of 418 articles were found using the following sets of keywords: Endophytic, fungi, and Cerrado; endophytic, fungi, rupestrian, and grass lands; endophytic, fungi, Brazilian, and savanna; among these, 14 articles were selected. The articles were grouped into studies on the biodiversity of Cerrado endophytic fungi, chemical studies, and other subjects. All the articles were found to be related to the diversity present in the Cerrado of the southeastern and midwestern regions, they show high fungal biodiversity with Diaporthe genus predominant in almost all plants studied. In all the studies on the chemical diversity of endophytic fungi, new compounds or new natural products were found associated with a range of bioactivity, especially antifungal. It shows the great potential of endophytes in the production of new and bioactive secondary metabolites, as well as the unexplored chemical diversity of endophytes isolated from endemic plant species. The review shows that rare studies performed in regions where the Cerrado biome are predominant, including the central, north, and northeast regions, representing an important niche that is still unexplored.