In recognition of its numerous medicinal benefits, bitter leaf (Vernonia amygdalina L.) is widely used in traditional medicine. Despite substantial research, a comprehensive comparative analysis of the antioxidants and phytochemical properties of its methanolic and aqueous extracts remains undocumented. This study addresses this gap by examining the differences in antioxidant values and phytochemical constituents between the two extracts using advanced analytical techniques. NMR and FTIR spectroscopy were employed to investigate probable phytochemicals, while HPLC and GC-MS determined the differences in biological components. Both DPPH and ABTS radical-scavenging tests evaluated variations in antioxidant activity. NMR Results indicated the presence of aromatic protons, phenolic hydroxyl groups, methyl groups, and methoxylated substances by the singlet signal at 7.1–7.5 ppm, singlet at 4.0–4.5 ppm, doublet at 1.0–1.5 ppm, and singlet at 2.0–2.5 ppm, respectively. FTIR results showed a C=O stretching at 1700 cm-1, an O-H stretching at about 3250 cm-1, and a C=C stretching between 1500 and 1600 cm-1. Methanolic extracts had higher phytochemical values according to GC-MS and HPLC data, except for rutin, delta-cadinene, and alpha-cadinol, which were higher in the aqueous extract. The methanolic extract exhibited superior antioxidant activity in DPPH and ABTS assays, with maximal scavenging activities of 90.5% and 96.8%, respectively. At 200 µg/mL, the aqueous extract demonstrated scavenging activities of 85.4% and 92.7%. These findings underscore the enhanced potential of methanolic extract for therapeutic applications.