Chromones (1-benzopyran-4-ones) and chromone derivatives are naturally occurring compounds ubiquitously found in the plant kingdom, and therefore present in representative amounts in a normal human diet. These phytochemicals possess a wide spectrum of biological activities — such as anti-inflammatory, antifungal, antimicrobial, antiviral, antitumour and anticancer — mainly due to their well-recognised antioxidant properties, which stem from their ability to neutralise active forms of oxygen and to cut off free radical processes. Since oxidative stress is known to be the basis for numerous severe pathologies, from cardiovascular and neurodegenerative disorders to cancer, the development of effective antioxidant agents from natural origin (namely dietary constituents) has been the object of vigorous research in the last decade, in view of establishing novel chemopreventive strategies against such diseases which are nowadays the main cause of death worldwide. In fact, the chromone moiety is an important element of pharmacophores of many biologically active molecules displaying diverse medicinal applications. These potential health benefits arising from the antioxidant activity of chromone derivatives are ruled by strict structure-activity/ structure-property relationships, which, apart from determining their biological action, modulate their systemic distribution and bioavailability in sites of oxidation within the cell. The present work aims at reviewing the main reported studies on the cytoprotective and anticancer activities of chromone derivatives, with particular emphasis on the effect of their structural features and conformational behaviour on activity, which is the basis of a tailored design of novel chromone-based antioxidants for chemopreventive and chemotherapeutic use.