Profiling of volatile and non-volatile compounds in stems and leaves of water spinach was performed using gas chromatography-flame ionization detector (GC-FID) and GC/mass spectrometry (MS) method after derivatization. Antioxidant activity was measured by both 1-diphenyl-2-picrylhydrazyl (DPPH) assay and Folin-Ciocalteu total phenol assay. Partial least squares regression (PLSR) was performed to determine the most important volatile and non-volatile compounds with antioxidant activity in both stem and leaf of water spinach. Phytosterol (26.97 and 19.78%), terpene (5.71 and 7.73%), phenolic compounds (3.87 and 2.66%) and Vit E (2.52 and 2.26%) were found to be major volatile compounds in both stem and leaf of water spinach, respectvely. Among the non-volatile compounds, significant amounts of amino acids (31.48 and 18.83%), sugar and sugar alcohol (32.17 and 18.58%), and fatty acids (7.07 and 26.39%) were found in stem and leaf of water spinach, respectively. DPPH free radical-scavenging effect in stem (92.11%) was higher than that in leaf (84.03%), whereas, electron-reducing capacity was higher in leaf (287.45 ${mu}g$ GAE/mL) than in stem (216.45 ${mu}g$ GAE/mL). Results show that water spinach exerts antioxidant activity via volatile compounds (phytosterol) in stems and non-volatile compounds (amino acids, acids, sugar alcohols) in leaves.