There has been considerable interest in commercializing fruits of Garcinia humilis due to its pleasant taste and nutritional quality. However, the industrial processing of the fruit generates the peel as waste and this study focussed on upcycling of the peel for its anti-melanoma activity at different extraction conditions (24 °C and 37 °C for 24 h, and 70 °C for 1 h). Although the extraction yield was highest at 70 °C, the phenolics and flavonoids extracted, and anti-cancer activity was highest when extracted at 37 °C. Polyphenolic compounds including epicatechin, procyanidins, mangostanol, and gamma-mangostin were tentatively identified based on LC-Orbitrap MS/MS analysis. These extracts showed dose-dependent anti-melanoma activity on MM418C1 (BRAF mutated oncogene) and D24 (wild type BRAF oncogene) cells with IC₅₀ in the range of 130–200 μg/mL and 122–176 μg/mL. Furthermore, the extracts had little effect on control fibroblast cells, indicating selective activity on cancer cells, and displayed morphological changes indicative of apoptosis. Although these extracts were 10 fold less effective compared to anti-cancer drug controls, cisplatin and vemurafenib, the moderate anti-cancer activity of Garcinia peel provides future opportunities for upcycling of this discarded waste as a functional food ingredient.