Aims: This study aims to assess the effect of simultaneous use of cannabigerol (CBG) and 3-O-ethyl ascorbic acid (EAA) on changes in the skin melanocyte proteome induced by UVA radiation, with particular emphasis on modifications in the structure of metabolically important proteins. Results: Proteomic analysis allowed to identify 1248 proteins with statistically significantly changed expression following melanocytes irradiation and/or incubation with CBG/EAA. The top 25 proteins with most strongly modified expression included mainly proteins involved in cells protection/antioxidant response, as well as pro-inflammatory and proapoptotic signalization. Moreover, in melanocytes irradiated with UVA, the levels of lipid peroxidation product, 4-hydroxynonenal (4-HNE) and its protein adducts increase, as well as significant changes in the profile of proteins modified by 4-HNE are observed. CBG and EAA, especially when used together, largely reverse this effect. Innovation: This study for the first time shows the combined effect of CBG and EAA on the proteome of melanocytes after their exposure to UVA radiation, that applies to both changes in protein expression and intracellular signaling based on protein modification by lipid peroxidation products. Conclusion: It can be summarized that CBG and EAA can provide melanocytes with the most effective protection against oxidative stress, and perhaps even protect the skin structure against carcinogenesis.