| Summary: | Biological activity and bioactive compound content in sea cucumbers was assessed, considering <i>Parastichopus regalis</i>, <i>Holothuria mammata</i>, <i>Holothuria forskali</i>, and <i>Holothuria arguinensis</i> as species and intestine, muscle band, respiratory tree, body wall, and gonads as tissues. <i>P. regalis</i> had the lowest content in phenolic compounds and antioxidant activity in contrast to <i>Holothuria</i> species. In the respiratory tree, the highest phenolic concentration was recorded in <i>H. arguinensis</i>, 76.4 ± 1.2 mg GAE/100 g dw vs. 21.0–49.0 mg GAE/100 g dw in the other species. <i>H. arguinensis</i> had the highest DPPH and FRAP results in the gonads, 13.6 ± 0.7 mg AAE/100 g dw vs. 2.6–3.5 mg AAE/100 g dw and 27.1 ± 0.3 μmol Fe<sup>2+</sup>/g dw vs. 8.0–15.9 μmol Fe<sup>2+</sup>/g dw, respectively. Overall, <i>P. regalis</i> biomass presented the highest anti-inflammatory activity levels and <i>H. arguinensis</i> the lowest anti-inflammatory levels. The respiratory tree was the most anti-inflammatory (measured by the inhibition of cyclooxygenase-2, COX-2) tissue in <i>H. mammata</i> and <i>H. forskali</i> (also the muscle band in this case), 76.3 ± 6.3% and 59.5 ± 3.6% COX-2 inhibition in 1 mg/mL aqueous extracts, respectively. The results demonstrated a variable bioactive potential and advantage in targeting antioxidant properties in the muscle band and anti-inflammatory activity in the respiratory tree, which may constitute a starting point for a biorefinery approach envisaging multiple applications.
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