People worldwide encounter various diseases like cancer, diabetes, tuberculosis, and many more. In order to provide assistance and alleviation from these diseases, it is critical to extract new and beneficial compounds. Traditionally, medicinal plants have been used to extract bioactive compounds to cure a wide variety of diseases. The microbial communities of these plants are also capable of producing bioactive secondary metabolites, which are useful for medicinal purposes and also promote growth of the host plant. Due to the significant, economical, and environmentally beneficial contributions of endophytic fungi, researchers are actively working on isolation of endophytic fungi from unexplored plants and elucidating the biological potential of their wide variety of secondary metabolites. Some such fungal endophytes and their bioactive compounds are Aspergillus awamori from Acacia nilotica with potent antidiabetic property, Taxomyces andreanae from Taxus brevifolia showing anticancer activity, and Phomopsis sp. from Garcinia sp. with antituberculosis potential. This chapter provides an overview of the secondary metabolites produced by endophytic fungi and their use in the treatment of human illnesses.