Background: The leaves of Alpinia zerumbet var. excelsa (alpinia) are used to prepare traditional food items and folk medicines. Objective: This study was designed with a view to explore the anti-inflammatory and anti-melanogenic potentials of major components of alpinia leaves. Materials and Methods: Anti-inflammatory effects of leaf-derived compounds were primarily assessed with protein denaturation and proteinase assay. Their inhibitory effects on nitrite accumulation and prostaglandin E2 (PGE2) production in lipopolysaccharide-induced RAW 264.7 cells were also evaluated. For anti-melanogenic assays, all the compounds were tested on α-melanocyte-stimulating hormone-stimulated B16F10 cells and on mushroom tyrosinase in vitro. Their cytotoxicity was evaluated using fibroblast cell line 3T3 L-1 and brine shrimps. Results: Five compounds, 5,6-dehydrokawain, dihydro-5,6-dehydrokawain, (E)-5-methoxy-8-(4-methoxy-2-oxo-2H-pyran-6-yl)-7-phenyl-1-styryl-2-oxabicyclo[4.2.0]oct-4-en-3-one (AS-2), kaempferol 3-O-β-D-glucuronide (KOG), and quercetin 3-O-β-D-glucuronide (QOG) were purified from the leaves. Of which, AS-2 and QOG were purified for the first time. All compounds significantly inhibited albumin denaturation and proteinase activity. AS-2, KOG, and QOG remarkably inhibited nitric oxide formation with IC50 values of 8.2, 13.3, and 12.6 μM, respectively, in RAW 264.7 cells. They also inhibited PGE2 production with IC50 values 19.8-23.7 μM. They showed anti-melanogenic effects reducing tyrosinase activity (IC50 values 29.6-112.5 μM) and melanin formation (IC50 values 30.8–164.4 μM) in B16F10 cells, and inhibiting mushroom tyrosinase (IC50 values 61.5-456.4 μg/ml). Conclusion: Taken together, major components of alpinia leaf could be utilized as a potent herbal drug and food supplement with therapeutic prospects against inflammatory disorders and hyperpigmentation.