Global terrestrial plant biodiversity remains a largely untapped source of natural bioactive compounds. In fact, valid sources are even “hiding in plain sight”, yet not “within reach” due to lack of effective technical solutions to unlock their potential. In this context, the PROSPLIGN consortium has developed an innovative bioprospecting approach that uses cutting-edge and complementary chemical and enzymatic methods, supported by statistical analysis and coupled with high-throughput detection methods, to enable the discovery of bioactive molecules from lignin, one of the fractions of the most abundant biopolymer on Earth (lignocellulose). Lignin “chemical biodiversity” will enable PROSPLIGN to cover three target markets (pharmaceuticals, cosmetics and fragrances) with a combined market of >€1.4 trillion. The project will use lignin derived from 9 different species and investigate at least 3 different chemical approaches and 10 different enzymes to obtain up to 1000 mixtures of lignin-derived compounds, and then pass a progressively narrower “hit validation funnel” in industrially relevant environments, being screened via up to 17 different bioactivity assays. Sustainable production routes for at least 2 of the most promising compounds per sector, directly or following derivatisation, will be proposed. Compared to traditional approaches, PROSPLIGN's bioprospecting avoids animal cruelty, expensive exploration efforts (no novel animal/plants discovery), disruptive extractions (seeking “hidden gems” in an abundant but underexploited “biomass mine”), and directly targets the liberation of readily testable bio/chemical-functionality present in plant material, superior to other approaches relying on “manipulation-intensive” microbial strain culture or “extrapolation” from DNA/RNA). Ultimately, PROSPLIGN will contribute to a new generation of biobased bioactives, unlocking more value from existing sources whose immense potential has yet to be harnessed.