My research activity during the thesis and training period was focused on the study of Arbutus unedo L., spontaneous plant of the Mediterranean scrub, carried out with a view to its enhancement and possible increase of its cultivation, as it is resistant to high temperatures, high solar radiation and low water availability. The leaves of this species are especially rich in polyphenols. These secondary metabolites possess multiple benefits for human health, thanks to their antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The objective of this research was to study a native Mediterranean shrub, Arbutus unedo L., generally known as the strawberry tree, in view of its sustainable cultivation to produce leaf polyphenolic extracts. The first part was conducted to search an optimized model for the extraction of polyphenols from the leaves of this species, using a “green” methodology. Secondly, we compared the extracts obtained from the cultivation of the species under two irrigation regimes (well-irrigated and non-irrigated plants) on a seasonal level. These analyses were carried out in a farm located in Maremma, collecting Arbutus unedo L. leaves in July and October, and monitoring the physiological state of the plants through the assessment of the leaf relative water content (RWC), chlorophyll fluorescence and the use of Dualex® (to measure chlorophyll and flavonoid indices). The collected leaves were then extracted with the green optimized protocol and subsequently analyzed by HPLC-DAD. Through this work, we could optimize the extraction of polyphenols from A. unedo L., reducing the extraction time and the consumed energy of the process. Furthermore, the cultivated plants showed the highest content of leaf metabolites in October after the application of the water stress treatment.