The growing threat arises due to diseases such as cancer and the infections around the world leading to a critical requirement for novel and constructive compounds with unique ways of action capable of combating these deadly diseases. At present, it is evident that endophytic fungi constitute an enormous as well as comparatively untapped source of great biodiversity that can be considered as a wellspring of effective novel natural products for medical, agricultural and industrial use. Marine endophytic fungi have been found in every marine plants (algae, seagrass, driftwood, mangrove plants), marine vertebrates (mainly, fish) or marine invertebrates (mainly, sponge and coral) inter- and intra-cellular without causing any palpable symptoms of illness. Since evolution of microbes and eukaryotes to a higher level, coevolution has resulted in specific interaction mechanisms. Endophytic fungi are known to influence the life cycle and are necessary for the homeostasis of their eukaryotic hosts and the chemical signals of their host have been shown to activate gene expression in endophytes to induce expression of endophytic secondary metabolites. Marine endophytic fungi are receiving increasing attention by chemists because of their varied and structurally unmatched compounds that have strong biological roles in life as lead pharmaceutical compounds, including anticancer, antiviral, insulin mimetic, antineurodegenerative, antimicrobial, antioxidant and immuno-suppressant compounds. Moreover, fungal endophytes proved to have different biological activities for exploitation in the environmental and agricultural sustainability.