The oxidative hair dye is the most expressive within this category and most contain the dye precursor p-phenylenediamine (PPD) and a coupling agent such as Resorcinol (RCN) which, after successive reactions under oxidative conditions, result in coloring of the hair. PPD is often used to contribute to the development of the final color, especially for dark shades. Exposure of the skin to this compound, in addition to irritation, can cause acute, subacute or chronic allergic contact dermatitis and induce the generation of reactive oxygen species (ROS), exacerbating the immune response and contributing to the impairment of the epidermal barrier. A good strategy to help prevent these symptoms is to associate an effective cosmetic ingredient with coloring to protect the scalp, avoiding or reducing the side effects of this inflammatory process. The use of natural ingredients in cosmetics is growing every year, therefore, the association of antioxidant and anti-inflammatory properties of plants can be an interesting approach to mitigate allergic effects. Ilex guayusa leaf extract is an emblematic tree of the Amazon region, widely present in the region of Ecuador, Colombia, Peru and Bolivia with various uses in folk medicine, however, there are only few researches about the phytochemistry and biological activities in different applications such as nutraceutical or cosmetic. The objective of this study was to explore the effectiveness of dry leaf extract of ilex Guayusa as protective agent against inflammatory response and exacerbated oxidative stress, recovery of epidermal barrier and reduction of sensitivity in the scalp promoted by hair color. For this, the study was conducted in three steps: in vitro, ex vivo, clinic. In the first step, cells from hair follicle dermal papilla (HFDPCs) were incubated with 3 non-cytotoxic concentrations of the product concomitant exposure to chemical inducers (0.01µM PPD and RCN + 3% H2O2) for further evaluation of radical protein formation and radical status factor (RSF), semi-quantitative assessment of mitochondrial super oxide using the fluorogenic probe MitoSOX ™ Red and quantification of the interleukin 8 (IL-8). In the second step, two Guayusa concentrations (0.5% and 1%) were prepared directly in the hair dye and evaluated in ex vivo scalp fragments culture and human hair shaft submitted to the dyeing process. In the third stage, a single-center, blind, comparative clinical study was conducted to prove the effectiveness of using 0.5% Guayusa in reducing scalp sensitivity induced by hair dye. Our results demonstrate that Guayusa can reduce the excessive synthesis of IL-8, an important inflammatory marker of the allergic contact dermatitis process, and recovers the epidermal barrier, strengthening the synthesis of filaggrin. In addition, reduces mitochondrial oxidative stress and protect the scalp and hair shaft from the action of free radicals, increasing hair strengthen and hydration effect. Clinically, we observed a reduction in scalp sensitization. These results together demonstrate that the use of Guayusa associated with hair coloring protects the scalp and hair shaft from damage caused by chemical inducers commonly present in hair colorings, improving consumer health and well-being.