Cellulosic fabrics made of cotton, linen, bamboo, hemp, and nettle, were selected for the eco-sustainable production of colored biofunctional textiles, using natural dyes from onion skin of the Dorata di Parma (Allium cepa L.) variety. Dyeing experiments were performed in net water with and without pre-treatment with alum, tin chloride, and tannic acid as mordants. The color and the UV-protection factor (UPF) were evaluated through UV–visible spectroscopy. The treatment with onion skin extract induced a relevant increase of UPF in all investigated fabrics, promoting the protection category from insufficient (UPF<15) to good for linen (UPF = 21–26), up to very good and excellent for cotton (UPF = 35–66) and bamboo (UPF = 48–56), respectively. To mimic the direct contact with the skin, textile samples were immersed in artificial sweat where dyed cotton, hemp, and nettle were found to promote higher phenolic release (0.28–0.50 mg gallic acid equivalents/g textile) than linen and bamboo (0.12–0.22 mg gallic acid equivalents/g textile). The obtained “biofunctional sweat” did not impact on the survival of primary human dermal fibroblasts (HDF) and skin keratinocytes (NCTC2455), while protected these cells against heat shock and reduced reactive oxygen species levels upon exposure to pro-oxidant and inflammatory agents as H2O2 and lipopolysaccharide, respectively. Increased activity levels of the H2O2-scavenging enzyme Catalase (CAT) were also observed, thus demonstrating enhanced stress response and homeostatic capability of these cells. This study provides evidence that extracts from onion waste can be used to functionalize cellulosic fabrics conferring properties as natural shield against UV radiation, and antioxidant and anti-inflammatory materials thus holding potential in skin protection and prevention of dermatological diseases. •Onion skin is used for the sustainable coloration of organic cellulosic fabrics.•Dyed cotton, bamboo and linen ensure good to excellent protection from UV radiations.•Dyed nettle, hemp and cotton release higher content of phenols in artificial sweat.•Biofunctional properties of dyed textiles are assessed in vitro on dermal cells.•The phenols released by dyed textiles decreased ROS in H2O2 and heat shock stress skin models.