Members of Achilllea L. genus are widely used against dermatological disorders in traditional medicine. An increasing number of experimental studies indicated that these species are an important source of ailments against such conditions. Besides, clinical studies yield supportive results about the dermatological effects of the genus. However, the number of studies stating the mechanisms of actions is quite scarce. A. clypeolata Sn. grows naturally in the Thrace region of Turkiye, and is used against various health problems in folk medicine. The methanolic extract prepared from the aerial parts of the plant (ACM) was subjected to a series of tests focusing on the mechanisms of dermatological activity. First, in vitro antioxidant screening tests, including DPPH, CUPRAC, FRAP and TOAC were applied. Then, the inhibitory potential of ACM against skin-related enzymes such as collagenase, elastase and hyaluronidase was measured. For a more detailed profiling of the activity, human dermal fibroblast cells (HDFs) treated with H2O2 were given varying concentrations of ACM. WST-1 analysis was carried out for the assessment of cell viability, and DCFDA (2′,7′-dichlorofluorescin diacetate) method was employed for the measurement of cellular antioxidant activity. In addition, the inhibitory potentials of ACM against matrix metalloproteinase -2 and -9 enzymes, which are responsible for the degradation of extracellular matrix components in the skin, were also tested. The total phenolic (26.02 ± 1.04 mg GAE/g dry extract) and flavonoid (12.85 ± 0.69 mg QE/g dry extract) contents of ACM were calculated with the activity tests. Also, for a comprehensive quantitative analysis, LC-MS/MS analysis was carried out. All of the data gained from the mentioned tests and analysis revealed the high capacity of ACM in dermatological conditions such as the inhibitory potential enzymes associated with skin aging. Phytochemical profiling studies showed that the extract is rich in phenolic compounds, specifically chlorogenic acid, hesperidin and hyperoside. Data obtained from this study suggest that A. clypeolata may act as a natural source of skin-active ingredients.