Klebsiella pneumoniae is a multidrug-resistant (MDR) pathogen causing hospital-acquired infections with up to 50 mortality. This study evaluates the antibacterial effects of Delphinium denudatum and Citrus limon aqueous extracts against K. pneumoniae, targeting key enzymes DapB, EntD, and MurG. Inhibiting DapB and MurG weakens the bacterial cell wall, while blocking EntD disrupts siderophore production, limiting iron uptake. Phytochemical screening, MTT assays, and antibacterial tests identified bioactive compounds in aqueous extracts. D. denudatum root extract showed a 28 ± 1 mm inhibition zone, and C. limon seed extract 24 ± 1 mm, exceeding imipenem, ceftazidime, and ciprofloxacin. Also, the extract showed no cytotoxicity to HEK293 cells. Virtual screening and molecular dynamics simulations identified panicutine and limonin as candidate inhibitors, with binding energies: DapB (�22.47, �25.46 kcal/mol), EntD (�14.7, �20.13 kcal/mol), and MurG (�14.15, �14.85 kcal/mol). This is the first report of these compounds as potential inhibitors, offering new treatment avenues for MDR K. pneumoniae. © 2025 Elsevier B.V., All rights reserved.