Since the nineteens, Uruguayan native forests have been protected by law and their utilization reduced to some scarce traditional uses if not literally left untouched in many cases. However, in the last years, discussions raised around the ecological significance and the socio-economic future of this natural patrimony and a new national strategy was designed with a quite wide stakeholders participation. In parallel, as part of a national prospective study, the government conducted a bioeconomy study, applied to both planted and native forests. Biorefinery, through the extraction of high-value molecules from non-wood products for green chemistry was identified as one of the challenging approaches to fulfill the expectations of the bioeconomy implementation in the country. This works reports the research advances obtained by the Forestry Department of the National Agricultural Research Institute (INIA-Uruguay) in the field of: (i) the identification, extraction and characterization of secondary metabolites of native forest species as a raw material for biomaterials production and (ii) the way to increase its production through high-value tree domestication for ex situ cultivation providing knowledge to improve the reproduction, growth and yield of promising forest species. Two target native forest species (Quillaja brasiliensis and Prosopis affinis) were systematically studied through an interdisciplinary agenda and with an interdisciplinary team, covering different steps from the field to the laboratory: bioprospecting, cutting and plant production in vitro, seedling propagation in nursery, laboratory extraction and characterization of secondary metabolites, industrial scaling up and diffusion and technology transfer.