Melanoma is a skin cancer that relies on angiogenesis for growth and progression. Angiogenesis is the growth of new vessels from existing vessels and follows a number of steps that include endothelial cell growth, migration and tubulogenesis. Current anti-angiogenic drugs are not effective in the treatment of melanomas due to serious side effects such as hypertension and the development of resistance. On the other hand, gold nanoparticles (AuNPs) have been reported to be biocompatible in preclinical models. Furthermore, AuNPs were shown to be cytotoxic to prostate cancer cells. In human umbilical vein endothelial cells, AuNPs inhibited the angiogenic protein, vascular endothelial growth factor-A (VEGF-A). Therefore, the study aimed to investigate the possible cytotoxic effects of AuNPs (1.2–3.2 nM) on melanoma cells and angiogenesis parameters (endothelial cell growth and migration) as well as on the levels of angiogenesis promoting proteins, VEGF-A and placental growth factor (PIGF). Melanoma (B16-F10) cells and tumour-derived endothelial (sEnd.2) cells were maintained in an incubator in a humidified atmosphere containing 5% CO2 at a temperature of 37°C. To investigate whether AuNPs were cytotoxic to melanoma cells, the effect of the particles on B16-F10 cell survival was measured using the crystal violet assay. To determine the effects of AuNPs on angiogenesis parameters, endothelial cell (EC) growth and migration were investigated using crystal violet assay and the scratch assay respectively. Also, EC morphology was studied using polarisation-optical interference contrast light microscopy. The enzyme-linked immunosorbent assay (ELISA) was used to determine the effects of AuNPs on the levels of VEGF-A and PIGF. The results showed that AuNPs decreased the viability of melanoma and endothelial cells. The scratch assay showed that more ECs migrated in cultured treated with AuNPs (P < 0.05). The concentration of VEGF-A and PIGF was reduced significantly following treatment with AuNPs, meaning that the particles exhibited anti-angiogenic properties. This outcome provides a basis for further testing of AuNPs as a potential treatment for melanoma.