Serenoa repens is a medicinal plant well-known for its therapeutic potential in treating various urological disorders and prevention of prostatic cancer. However, the extraction process in the pharmaceutical industry leads to the generation of plant residues, typically discarded, wasting valuable resources. In this study, we aimed to explore a series of green extraction strategies to effectively valorize the residues of Serenoa repens fruits. Initially, we employed supercritical CO2 (1.2% yield on dry biomass) on the discarded biomass to identify and quantify residual fatty acids and polyprenols (1.6% of the extract dry weight), a class of unsaturated isoprenoid alcohols with promising biomedical applications. Subsequently, subcritical water extraction was utilized on the exhausted biomass to extract polar compounds. An increase in the extraction yield was observed with the rise in processing temperature up to 180 C-degrees (yields were found higher than 26%). Phenolic compounds and carbohydrate macromolecules profiles were affected by the increased hydrolytic conditions. Polar extracts exhibited robust bioactivities, demonstrating significant antioxidant activity and antimicrobial efficacy against Gram-positive and Gram-negative bacteria strains. Extracts obtained at 180( degrees)C demonstrated the highest efficacy. Furthermore, in vitro assessment of mannans-rich fraction provided a new perspective of potential applications in the cosmeceuticals field. Results underscore the potential of the sustainable extraction biorefinery for the residue of this medicinal plant and demonstrate that, harnessing these bioactive compounds, new sustainable and eco-friendly approaches for its complete utilization can be offered, thereby promoting near-zero waste practices and contributing to a more sustainable future.