Fungi have a long and intimate connection with humankind, particularly at the chemical level as a source of both harmful and beneficial compounds. Their worldwide occurrence in various food and feeds poses a major health threatening risk for human and animal and, as a consequence, mycotoxins represent an economic burden. Fortunately, not all fungal secondary metabolites are toxic to humankind such as; antibiotics, phytotoxines, enzymes and antioxidants, which represent the other side of the coin. Endophytes are now considered as an important component of biodiversity, and act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, flavanoids, phenols, phenolic acids, quinones, steroids, saponins, tannins, terpenoids, isocoumarin derivatives, peptides and enzymes, beside their ability to produce the same or similar kind of compounds of their host plants. Today's world challenge is ensuring the safety of food, which has been a major focus of international and national action over the last years. Legislative limits for a range of mycotoxins continue to develop worldwide, due to being carcinogenic to animals and humans, resulting in an increased number of official controls monitoring in the food supply chain deriving from national food safety plans and for food trade purposes. This review brings about the harmful (mycotoxins) and beneficial (antioxidants, antibiotics, enzymes) fungal metabolites in industrial and pharmaceutical applications. It also provides a perspective about mechanism of how can endophytic fungi metabolites play a reverse role as one of the main strategies of mycotoxin deactivation and prevention representing the other side of the coin.