Coping with a zero-waste, more sustainable economy represents the biggest challenge for food market nowadays. We have previously demonstrated that by applying smart multidisciplinary waste management strategies to purple sea urchin (Paracentrotus lividus) food waste, it is possible to obtain both a high biocompatible collagen to produce novel skin substitutes and potent antioxidant pigments, namely polyhydroxynapthoquinones (PHNQs). Herein, we have analyzed the biological activities of the PHNQs extract, composed of Spinochrome A and B, on human skin fibroblast cells to explore their future applicability in the treatment of non-healing skin wounds with the objective of overcoming the excessive oxidative stress that hinders wound tissue regeneration. Our results clearly demonstrate that the antioxidant activity of PHNQs is not restricted to their ability to scavenge reactive oxygen species; rather, it can be traced back to an upregulating effect on the expression of superoxide dismutase 1, one of the major components of the endogenous antioxidant enzymes defense system. In addition, the PHNQs extract, in combination with Antimycin A, displayed a synergistic pro-apoptotic effect, envisaging its possible employment against chemoresistance in cancer treatments. Overall, this study highlights the validity of a zero-waste approach in the seafood chain to obtain high-value products, which, in turn, may be exploited for different biomedical applications.