Endophytic fungi residing in medicinal plants have the ability to produce the same pharmacologic bioactive secondary metabolites as their host medicinal plants, which have been used for thousands of years in traditional medicine and still are used for their health benefits. Nowadays, medicinal plants are quarrying for isolation of plant-derived drugs as they are very effective and have reasonably less or no side effects. However, the natural resources of ethanomedicinal plants are gradually exhausted and access to plant bioactive compounds is challenged by the low levels at which these products accumulate in native medicinal plants. For example, to meet the market demands of 3 Kg per year of Vinca alkaloids, powerful plant-derived anticancer drugs, 1.5x10⁶ Kg dry leaves are required. In this regard, this review articles aims to highlight the fact that endophytic fungi residing in medicinal plants are capable to biosynthesize pharmacologically active secondary metabolites as antioxidant identical to those produced by their host medicinal plant. Furthermore, the evolutionary origin of the genes involved in these metabolic pathways as well as the approaches designed to enhance the production of these secondary metabolites by the isolated endophytic fungi medicinal plant have a lot of type of antioxidant mostly polyphenols, flavonoids which exhibit high antioxidants bioactivity. In addition to aforementioned reasons, this article also will shed the light on the efforts of Abdel-Azeem and his co-workers at Botany department, Faculty of Science, Suez Canal University and their continuing search for biologically active natural products from Egyptian endophytic fungi hosted medicinal plants in Saint Katherine Protectorate, Arid Sinai, Egypt.