Endophytic fungi, which reside in medicinal plants, are considered potential sources of therapeutic production by mimicking the host plant metabolisms. Additionally, they have the capability to produce novel metabolites through complex gene expression. Endophytes, their crude extracts, or active molecules derived from them are employed for plant protection, particularly against plant pathogenic viruses. The utilization of biological agents such as endophytic fungi in disease management and the development of agricultural systems, as opposed to chemical agents, is deemed environmentally safe. Recognizing the significance of endophytes, numerous studies have been conducted. Therefore, this book chapter explores the discussion of endophytes and their active molecules, specifically exploring their antiviral properties against plant viruses, methods for identifying active molecules, molecular mechanisms underlying the inhibition of pathogens, agricultural applications of endophytes and their derivatives, biotechnological approaches in novel metabolite production from endophytes, environmental safety, challenges in the application of endophytes, and potential future applications.