© 2021 Elsevier LtdMelanoma is a highly malignant tumor caused by melanocytes. Even though melanoma represents just 3% of all skin malignancies, it represents 75% of deaths. Extracts of A. hierchuntica were reported to have anti-inflammatory, hepatoprotective, and anti-melanogenic activities. This study aims to investigate the dose-related relationship and selectivity of the toxic effects of A. hierchuntica extracts (AHE) on melanoma cells and provide a new option that can be used in the future treatment of melanoma. B16F10 Mus musculus malign melanoma cells and L929 Mus musculus healthy fibroblast cells were treated with root and leaf AHEs in a dose-dependent manner. Intracellular glutathione levels, mitochondrial membrane potential activity, apoptosis, genotoxicity, and cytotoxicity of AHE were evaluated. This study is probably the first study to show a significant apoptotic and genotoxic activity of AHE in selected B16F10 cancer cell lines. Mitochondrial membrane potential and glutathione activity of B16F10 and L929 melanoma cells decreased with increasing concentrations of both leaf and root AHEs. However, viability and reactive oxygen species levels showed selectivity especially the AHEs concentrations between 400 μg/mL and 500 μg/mL. This selectivity based on doses was also validated in apoptosis and genotoxicity between healthy and cancer cells (p < 0.001). The results showed that when looking at melanoma-specific, AHE could be a source of inspiration as an active ingredient in future treatment protocols. AHE can be recommended as potential nutraceuticals in the prevention of human melanoma cancer.