Carboxymethyl cellulose is the most used water-soluble cellulose with applications in industries such as food, cosmetics, and tissue engineering. However, due to a perceived lack of biological activity, carboxymethyl cellulose is mostly used as a structural element. As such, this work sought to investigate whether CMC possesses relevant biological properties that could grant it added value as a cosmeceutical ingredient in future skincare formulations. To that end, CMC samples (M_w between 471 and 322 kDa) skin cell cytotoxicity, impact upon pro-collagen I α I production, and inflammatory response were evaluated. Results showed that samples were not cytotoxic towards HaCat and HDFa up to 10 mg/mL while simultaneously promoting intracellular production of pro-collagen I α I up by 228% relative to the basal metabolism, which appeared to be related to the highest DS and M_w. Additionally, CMC samples modulated HaCat immune response as they decreased by ca. 1.4-fold IL-8 production and increased IL-6 levels by ca. five fold. Despite this increase, only two samples presented IL-6 levels similar to those of the inflammation control. Considering these results, CMC showed potential to be a more natural alternative to traditional bioactive cosmetic ingredients and, as it is capable of being a bioactive and structural ingredient, it may play a key role in future skincare formulations.