In this study, Compritol ATO-based Resveratrol colloidal carriers (CCCs) were prepared and subjected to characterization and evaluation. In most formulae, the use of a binary-mixture of surfactants improved the physicochemical properties. CCC6 (containing P407/P188 as bi-surfactants) attained the highest drug loading, release efficiency during 24h and occlusive effect for 48h; in addition, it showed a uniform particle size distribution within the desired range. In-vivo studies were done based on the analysis of anti-oxidant markers [catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD)], anti-inflammatory markers [interleukin 6 (IL-6), interleukin 8 (IL-8) and rat Nuclear factor-kappa B (NF-κB)] and anti-wrinkling markers [matrix metalloproteinase (MMP-1) and Granulocyte-macrophage colony-stimulating factor (GM-CSF)], after UVB-irradiation. Results were significantly different when comparing the positive control and the negative control groups (p<0.05). Rats pre-treated with CCC6 showed a great amelioration, and the level of the biochemical markers was significantly different compared to those of the positive control group and those pre-treated with the drug suspension (p<0.05). Also, the high skin protective effect of CCC6 was proved by visual and histopathological examination of the rats’ skin. Therefore, the current study proves the beneficial effects of the designed dermal Resveratrol-loaded colloidal system.