Skin functionalities are instrumental in four main domains: protection, regulation, sensation, and support. However, excessive exposure to ultraviolet (UV) radiation can compromise skin integrity and, in turn, affect its functions, by generating reactive oxygen species (ROS). Aiming to protect skin from UV radiation, sunscreens incorporate UV filters and antioxidants that absorb/reflect UV rays and neutralise free radicals, respectively. Nevertheless, undesired side and ecological effects of conventional UV filters have spurred the search for safer alternatives. Among synthetic antioxidants, thioethers have attracted attention for their redox power and potential medicinal properties. In this context, a library of aminopyrimidine–arylthioether conjugates was synthesised and evaluated for their antioxidant, enzyme-inhibitory and antibacterial activities, as well as for their cytotoxicity in HaCaT cells and potential photoprotective properties. Among the aminopyrimidine-thioethers studied, compound C5 stood out for its antioxidant potential, exhibiting a value of 566.39 mM FeSO₄ equivalents per mM of the compound, while compound C2 showed the highest anti-enzymatic potential, inhibiting elastase (45.58%) and tyrosinase activities (34.66%). Regarding photoprotective activity, compound C13 reduced by 33.74% the ROS production induced by UV radiation exposure, at 100 μM, a non-cytotoxic concentration. Finally, compound C7 inhibited the growth of Staphylococcus epidermidis, Staphylococcus hominis and Cutibacterium acnes, at 30 μM. These preliminary results demonstrate that aminopyrimidine–arylthioethers constitute a new class of compounds warranting further investigation for skin protection. Compound C5 showed antioxidant activity in the FRAP assay, comparable to that of the positive control, BHT.