From the tropics to the arctic, almost all living plants on the earth are resided by endophytic fungi. The microorganism can be found near intercellular or intracellular tissues and cause void adverse symptoms of infection. Endophytes and host plants are synergistically protecting each other. As the host provides nutrients, the endophytes serve the host by activating their defense mode against parasites and pests. A search for alternative drugs, mostly from natural sources, is in ascending trends due to the increase of lethal diseases. This review emphasizes the significance of several endophytic fungi as a foundation for novel bioactive sources which might be advantageous for human health. The communication between the endophytic fungi and their host has generated numerous unique bioactive metabolites from different biosynthetic pathways. These include ketones, polyketides, alkaloids, non-alkaloids, acids, coumarins, etc., which comprise numerous potent biological activities including antimicrobial, anticancer, antioxidant, insecticidal, antidiabetic, immunosuppressive, anti-arthritis, anti-inflammatory, and anti hypercholesterolemic. Around 1.5 million endophytic fungal species have been estimated. However, to date, only 100,000 species are reported. Thus, a few isolated compounds and their biological activities have been opted in this current review. All compounds were discovered from endophytic fungi, which resided on various host plants, particularly from algae to a higher family plant such as mangroves. © 2021, University of Malaya. All rights reserved.