Acorns, the fruit of oak trees of the genus Quercus, have been known to people for generations worldwide. In ancient times, they were an important part of culinary traditions and folk medicine. Their exploitation for food over the years has been significantly diminished, which may arise from the high content of tannins responsible for a bitter taste and anti-nutritional properties. However, more and more studies show acorns’ potential nutritional and health benefits. Furthermore, new reports are emphasizing the health-promoting properties of tannin-decomposition products. This review aims to present the available studies on the phytoconstituents variation in the acorns of different Quercus species and their possible significance for food and medical applications. In this study, the results of lab-scale food processing, as well as in vivo and in vitro experiments, are included. The literature data proved that acorn products (flour, oil, and extracts) are intensively examined due to their dietary, antioxidant, anti-microbial, anti-inflammatory, anti-cancer, and neuroprotective activities provided by their bioactive compounds. The general conclusion is that this raw material can be used more widely in the future as an ingredient in functional foods, supplements, and drugs.