Endophytic microorganisms, which reside asymptomatically within plant tissues, have garnered significant attention for their potential as prolific producers of bioactive secondary metabolites. These compounds, including alkaloids, terpenoids, steroids, and phenols, exhibit a wide range of biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antioxidant properties. This review highlights recent advancements in the isolation, characterization, and application of bioactive metabolites derived from endophytic fungi and bacteria. Emphasis is placed on novel compounds discovered in the past decade, their biosynthetic pathways, and their therapeutic potential. Furthermore, the review delves into the symbiotic relationships between endophytes and their host plants, the role of these microorganisms in plant defense, and challenges associated with their study. The potential for endophytes in sustainable drug discovery and agriculture is also discussed.