Plant derived compounds show promise in addressing multi-drug resistance (MDR) in pathogens. This study evaluates Eclipta alba ethanolic extract for anti-MDR activity through integrated in vitro and in silico approaches. Phytochemical screening revealed abundant alkaloids, flavonoids, saponins, terpenoids, phenols, coumarins, and steroids, with quantified flavonoids (8.21 ± 0.53 mg QE/g) and phenolics (42.70 ± 1.85 mg GAE/g). GC-MS identified 20 compounds, including phytol (26.28%), ecliptalbine (11.07%), and stigmasterol (4.28%). The extract exhibited potent antioxidant activity (74.63% DPPH inhibition, 65.27% total antioxidant capacity at 160 µg/ml) and inhibited S. aureus, E. coli, and K. pneumoniae by 71–77%, rivalling tetracycline. Molecular docking highlighted beta-amyrin, oleanolic acid, and ecliptalbine as key agents, with binding affinities (–7.2 to –8.6 kcal/mol) surpassing tetracycline against bacterial targets. These findings validate E. alba’s traditional use and position its phytocompounds as novel candidates for developing antimicrobials to combat MDR, bridging ethnobotanical knowledge with modern drug discovery.
