Colocasia gigantea Hook f. (“Bon Khao” in Thai) is a traditional herb widely found in every region of Thailand. It has been regarded as a useful folk medicine with varied medicinal properties. This study aims to evaluate the cytotoxic effect of C. gigantea extract and gold nanoparticles toward A375 melanoma cell line. The effect of gold nanoparticles was studied together with C. gigantea extract since previous studies have reported the use of gold nanoparticles as a carrier to help deliver drug molecules into cells. MTT colorimetric assay was used in this study to assess percentage cell viability of the melanoma cells following treatments with C. gigantea extract, gold nanoparticles and their mixture (C. gigantea extract + gold nanoparticles) for 24 hours. Morphology of the melanoma cells was observed under light microscope. In addition, the mechanism of cell death was also studied by staining with annexin V and propidium iodide and analyzing under confocal microscope as well as with flow cytometer. The experimental result shows that C. gigantea extract, AuNPs and their mixture exhibit cytotoxic effect toward the melanoma cell line with statistical significance. The mixture of AuNPs and C. gigantea was found to be more effective than the mere treatment with AuNPs or C. gigantea extract of the same concentration alone. Following all treatments, the cells’ shape was also altered from a spindle-like shape to a more rounded one. From the analysis of flow cytometer results and confocal images, the major mechanism of cell death following all treatment conditions is by means of apoptosis.