The use of novel and helpful bioactive compounds is growing in today’s ever-changing world to address the many issues that humanity faces, such as environmental stress, biotic and abiotic stresses, water and food scarcity, the emergence of drug-resistant microbes, pollution, and rising rates of infections and diseases. Recent years have seen a rise in the worldwide concern for the development of more sustainable agriculture, and studies have been conducted to understand ecology and investigate the possibility of endophytic interactions in plant growth. Despite their lack of research, fungal endophytes are a powerful source of innovative natural compounds with applications in industry, agriculture, and medicine. About 10% of the world’s estimated one million plant species have been investigated to date for their remarkably diversified fungal endophytes. The array of bioactive metabolites generated by the fungal endophytes that have been explored so far is addressed in this chapter, with a focus on those that can be used to protect and enhance crops, with the goal to achieve sustainable agriculture.