Disorganization and breakdown of extracellular matrix proteins like fibronectin, collagen, and elastin are key characteristics of skin aging due to the increased activation of important proteolytic enzymes like elastases and collagenase enzymes. Also, inhibition of their enzymatic activities by natural molecules might be a promising factor to prevent extrinsic skin aging. All chemicals were obtained from Sigma-Aldrich unless otherwise stated. The assay employed was based on spectrophotometric methods reported in the literature. The collagenase and elastase inhibition assays of some phenolic compounds were performed according to the previous studies. These compounds showed excellent to good inhibitory activities of vulpinic acid against studied these enzymes with IC50 values of 195.36 µM for collagenase and 25.24 µM for elastase. The molecular docking calculations were conducted to investigate the chemical and biological activity of vulpinic acid and usnic acid against collagenase and elastase. The results indicated that these two compounds can interact with the essential residues of the enzymes and affect their activities. The calculations of binding free energies were also performed to obtain more details about the characteristics and free energies of the ligand-enzyme complexes. Additionally, both compounds exhibited the most potent inhibition in the three lung cancer cells, with an IC50 value of 21-68 µM, indicating that vulpinic acid is more potent than Doxorubicin, which exhibited an IC50 value of 21-29 µM.