This study employed an untargeted metabolomic approach combined with chemometrics to investigate differences in the phytochemical composition of Cecropia peltata samples collected on the mainland and islands of the Panamanian Pacific. Twenty-three samples of C. peltata leaves were collected and analyzed using liquid chromatography-high resolution mass spectrometry analysis (LC-HRESI-MS). The results revealed a significant diversity of secondary metabolites. A supervised chemometric analysis model (OPLS-DA) was applied to differentiate specimens collected on the mainland from those collected on the islands. Among the metabolites identified as potential chemical markers in the studied specimens, five belong to the group of triterpenoid saponins. These compounds showed a significantly higher relative abundance in samples collected on the mainland than those collected on islands. In conclusion, this study highlights the chemical variability within C. peltata based on its geographic location. The findings suggest the importance of considering geographic origin when evaluating the therapeutic potential of this plant species in traditional and pharmaceutical medicine.