The proliferation and coastal accumulation of the invasive alga Rugulopteryx okamurae has become a significant environmental and socioeconomic challenge. To mitigate such negative effects, great efforts are being made for the valorization of this biomass through the recovery of added-value bioactive compounds. However, for its effective transfer to the productive sector, the development of sustainable extraction methods and further in-depth characterization of the resulting extracts in chemical and functional terms is crucial to foresee feasible applications. Herein, we applied a Box-Behnken experimental design to optimize an ultrasound-assisted approach for the extraction of beach-cast seaweeds. A series of spectrophotometric assays were then employed to determine the contents of major phytochemical classes (polyphenols, flavonoids, phlorotannins, pigments) and in vitro biological properties (antioxidant and anti-inflammatory activity), in combination with cutting-edge metabolomics for exhaustive biochemical profiling. Optimal recovery yields were achieved by sonicating for 45 min at 60 ºC, using ethanol (55%, v/v) as extractant at a solvent-to-sample ratio of 25 mL/g. Interestingly, the method greenness was found to be superior to that reported in previous studies, as assessed through the AGREEprep metrics (score = 0.75). These extraction conditions enabled us to recover multiple health-promoting compounds, such as polyphenols (majorly phenolic acids, but also flavonoids, phlorotannins, and bromophenols), carotenoids (e.g., fucoxanthin), phytosterols (e.g., fucosterol), vitamins (majorly retinoids, but also B-group and antioxidant vitamins), polyunsaturated fatty acids (good n-6/n-3 balance), and amino acids (including essential species). As a result of this favorable composition, the extracts were proven to exhibit potent antioxidant and anti-inflammatory activity. Altogether, these findings highlight the potential of the environmentally-friendly and cost-effective ultrasound-assisted extraction method developed here to valorize R. okamurae through the elaboration of bioactive-rich and functional extracts.