Tabebuia is the largest genus among the family Bignoniaceae. Tabebuia species are known for their high ornamental and curative value. Here, the cytotoxic potential of extracts from the leaves and stems of five Tabebuia species was analyzed. The highest activity was observed for T. rosea (Bertol.) DC. stem extract against HepG2 cell line (IC50 4.7 µg/mL), T. pallida L. stem extract against MCF-7 cell line (IC50 6.3 µg/mL), and T. pulcherrima stem extract against CACO2 cell line (IC50 2.6 µg/mL). Metabolic profiling of the ten extracts using liquid chromatography-high-resolution mass spectrometry for dereplication purposes led to annotation of forty compounds belonging to different chemical classes. Among the annotated compounds, irridoids represent the major class. Principle component analysis (PCA) was applied to test the similarity and variability among the tested species and the score plot showed similar chemical profiling between the leaves and stems of both T. pulcherrima and T. pallida L. and unique chemical profiling among T. rosea (Bertol.) DC., T. argentea Britton, and T. guayacan (Seem.) Hemsl. leaf extracts and the stem extract of T. rosea (Bertol.) DC. Additionally, a molecular correlation analysis was used to annotate the bioactive cytotoxic metabolites in the extracts and correlate between their chemical and biological profiles.