<p>Phenolic compounds are a class of compounds with a wide range of positive biological functions and are the main pigment components in various natural-colored fibers. Common representative fibers containing phenolic compounds include white silk, green silk, brown cotton, and green cotton. The comprehensive antioxidant capacity of these fibers depends on both the content and properties of their phenolic constituents. Furthermore, the solubility of phenols influences the potential dermal absorption of pigments during wear. Given that phenolics in natural fibers may exert distinct effects upon skin contact, we optimized a method for quantifying the molar concentration of phenolic mixtures to systematically compare the physicochemical and biological impacts of phenols derived from different fibers. From the fiber perspective, green silk has the strongest antioxidant activity, which is related to its extremely high phenolic content. However, when evaluated at equivalent molar concentrations, phenols extracted from white silk demonstrated the highest free radical scavenging rate. Utilizing the molar concentration quantification method for further research, phenols in silk and green cotton have no significant toxicity to normal cells. Meanwhile, phenols from green silk and brown cotton significantly inhibited malignant melanoma cell growth. Comprehensive analysis indicates that among phenolic-containing fibers, green silk represents a material combining non-toxicity with potent antioxidant and anticancer properties.</p>