Salt stress is the most devastating abiotic stress that drastically limits the productivity and quality of crops. This study assessed the impact of NaCl concentrations (100, 200, and 400 mM) on betel vine's antioxidant activities and secondary metabolites (Piper betle L.). Results of the study suggest that the activity of antioxidative enzymes was enhanced at 100 and 200 mM NaCl levels but reduced at 400 mM NaCl. Further, the GC-MS analysis revealed the increased production of secondary metabolites such as alkane, ester, fatty acid, phenolic, and terpene compounds during salt stress. These findings would be helpful for further investigations that could lead to enhanced production of secondary metabolites in betel vine for industrial and medicinal benefits.