Antinutrients, also known as anti-nutritional factors (ANFs), are compounds found in many plant-based foods that can limit the bioavailability of nutrients or can act as precursors to toxic substances. ANFs have controversial effects on human health, depending mainly on their concentration. While the positive effects of these compounds are well documented, the dangers they pose and the approaches to avoid them have not been discussed to the same extent. There is no dispute that many ANFs negatively alter the absorption of vitamins, minerals, and proteins in addition to inhibiting some enzyme activities, thus negatively affecting the bioavailability of nutrients in the human body. This review discusses the chemical properties, plant bioavailability, and deleterious effects of anti-minerals (phytates and oxalates), glycosides (cyanogenic glycosides and saponins), polyphenols (tannins), and proteinaceous ANFs (enzyme inhibitors and lectins). The focus of this study is on the possibility of controlling the amount of ANF in food through fermentation. An overview of the most common biochemical pathways for their microbial reduction is provided, showing the genetic basis of these phenomena, including the active enzymes, the optimal conditions of action, and some data on the regulation of their synthesis.