This study investigated the metabolic profiles and antibacterial activities of Parkinsonia aculeata leaves, stems, and fruits. Butanol extracts were analyzed using LC-ESI-MS/MS, tentatively identifying 116 secondary metabolites based on fragmentation patterns, biosynthetic pathways, and literature comparisons. Spectral similarity networks generated through the Global Natural Products Social Network (GNPS) revealed chemical similarities and identified 6 uncommon flavone compounds. Spectral similarity analysis revealed a close chemical resemblance between leaves and stems, while fruits exhibited distinct profiles. Antibacterial activity was assessed against seven pathogenic strains using both disk diffusion and microbroth dilution methods. Leaf extracts demonstrated the strongest activity, with inhibition zones up to 20.13 mm and MIC values as low as 1.5 mg mL −1 , particularly against S. aureus ATCC 29213. Stem extracts showed comparable efficacy, while fruit extracts were more effective against K. pneumoniae. These findings highlight P. aculeata as a promising natural source of bioactive compounds for potential antimicrobial applications.