The olive tree is currently cultivated worldwide, with higher incidence in Mediterranean Basin. Its climate is highly favorable to the synthesis of phenolic compounds, stored in olive leaves; their consumption has been linked to a lower incidence of cancer and cardiovascular disorders for which the research interest upon this feature has increased in last decade. This study aimed (i) to review evidence about the importance of olive leaf extract (OLE) on human health and the physiological effect of its major compounds; (ii) to update the state of the art of studies conducted on the health and technological usage of olive leaf extract; (iii) to report potential uses of OLE in pharmaceuticals, food production, and cosmetics; and (iv) to prospect the future of clinical applications of OLE from diverse cultivars, especially in metabolic inflammatory conditions such as polycystic ovary syndrome (PCOS). Overall, cultivars richer in TPC, including TFC, αT, omega-3 and omega-9, present a main research target for supplementation alone or in conjunction with vitaminic compounds, due to their nutraceutical value in metabolic disorders, chronic inflammatory diseases, and anti-aging treatments, whereas cultivars with less water content might be useful as substrates for food preservation. With regard to future prospects, it would be of great interest to clarify the specific mechanisms underlying the beneficial effects of OLE on neuro-immune and cardiovascular health to design safer and healthier nature-based medicine for a wide array of costly and highly prevalent chronic diseases, such as inflammatory and metabolic-related syndromes, namely, PCOS.