This study investigated the antihyperglycemic potential of a hydroalcoholic extract from Syzygium malaccense leaves (E-SM) and isolate phenolic compounds with antioxidant and cytotoxic activities through a bioguided assay. The aim was to explore the therapeutic properties of S. malaccense in managing hyperglycemia and oxidative stress-related conditions. E-SM was prepared using ethanol-water (40:60 v/v) and purified through a solid-liquid procedure with increasing polarity solvents, yielding the acetone fraction (AceFr). Previous studies showed Ace-Fr had potent antioxidant and cytotoxic properties. Chromatographic techniques further purified AceFr, producing three bioactive subfractions (SF-1, SF-2, and SF-3). Flavonoids myricitrin (C1) and a mixture of quercitrin and mearnsitrin (M1) were isolated from SF-2 and SF-3 using TLC preparative. HPLC-DAD quantified phenolic compounds, including myricitrin, gallic acid, myricetin, and quercetin. HPLC-ESI-QTOF-MS/MS analysis identified ten compounds, primarily flavonols quercetin and myricetin and their glycosides. SF-1 exhibited a 30 % reduction in cell viability in cutaneous melanoma cells at 100 and 250 mg L