Melanoma is the most aggressive and deadliest type of skin cancer. Melanoma cancer develops in the melanocyte cells, which help in the body's pigmentation. The common cause of this cancer is ultraviolet radiation, which mutates and damages the DNA of skin cells and triggers the uncontrolled growth of melanoma cells. The fourth stage of melanoma is more prone to develop cancer in other organs such as the lungs, liver, and brain. No drug is available to cure the fourth stage of melanoma cancer and its lethal metastasis. Artemisinin is a well-established drug against malaria with drug-resistant strains. The previous report shows the role of Artemisinin in various neurodegenerative diseases like recently published study revealed that Artemisinin protects from hydrogen peroxide-induced oxidative damage in human retinal cells via activation of ERK/CREB signaling. Artemisinin also showed neuroprotection in PC12 and cortical neurons exposed to sodium nitroprusside-induced oxidative insult. DHA, another derivative of Artemisinin research in colorectal cancer, revealed that DHA inhibits HCT-116 cell proliferation in both concentration and time-dependent manner. DHA also caused apoptosis in HCt-116 cells through ROS mechanism pathways. So Artemisinin has a remarkable effect in cancerous and non-cancerous studies. But the role of Artemisinin in the cell proliferation, migration, and invasion in B-16, A375, and UM melanoma cells is not well known. The P13K/Akt pathway is mainly activated in melanoma tumors, and the increased level of AKT phosphorylation is linked with poor prognosis in various melanomas. In this present study, we explored the role of Artemisinin in B-16, A375, and UM melanoma cancer. We checked the effect of Artemisinin in the migration, invasion, and cellular proliferation of all different melanoma cells. We also check the anti-metastatic and anti-angiogenic properties of Artemisinin in melanoma cells. Our study results suggest that Artemisinin significantly inhibited the migration, invasion, colony formation, and angiogenic properties of B-16, A375, and UM melanoma cells. Artemisinin inhibited tumor growth in vivo in the B-16 subcutaneous tumor model, in correlation with a significant decrease of MMP-9, MMP2, CD31, and Ki67 tumor biomarkers levels.