Cancer, one of the leading causes of death, has seen progress in the development of drugs for intervention. However, these drugs often come with severe side effects. As a result, there has been a growing interest in functional food and natural products for their potential as anti-cancer therapies. One such example is orange peels (OPs) and their derived extracts, which demonstrate strong anti-cancer properties due to their high flavonoid content. OPs contain numerous bioactive compounds that can be used in drug development. This study aimed to isolate flavonoids from OPs and assess their anti-cancer potential against Hep-G2 cancer cells. High-performance liquid chromatography (HPLC) analysis revealed 19 flavonoid compounds in OPs, with chrysin, kaempferol, and catechin being the major constituents. The alcoholic extract of OPs exhibited antioxidant potential against ABTS and DPPH. Six flavonoids were isolated from citrus peel. These are: Kaempferol-3-O-rutinoside(nicotiflorin), Isorhamnetin-3-O-B-rutinoside, Rutin, Qercetin-3-O-β-glucoside, Isorhamnetin and hesperdin. The isolated compounds exhibited higher levels of cytotoxicity to cancer cells. These findings support the use of OPs as potential anticancer agents.