Abstract: The incidence of malignant melanoma, a highly fatal skin tumor, is on the rise worldwide. Melanomas are highly aggressive and have strong metastatic capability that leads to lethality. Recurrence occurs in patients with distant metastases, even with the latest treatments, and median survival is only a few months. At present, the prevention and treatment of melanoma includes surgical resection, chemotherapy, immunotherapy and targeted therapy. However, these strategies can lead to drug resistance and adverse effects. In recent years, an increasing number of studies have found that natural products have effective anti-melanoma activities, including inhibition of tumor growth, induction of cell apoptosis, inhibition of angiogenesis and metastasis and toxicity to tumor stem cells. In addition, several studies have reported that the combination of natural products and traditional anti-melanoma drugs can enhance the therapeutic efficacy. In this review we summarize the prevention and treatment of melanoma with natural products.