The rise of antibiotic resistance in pneumonia therapy highlights the urgent need for alternative treatments derived from natural sources. Azadirachta indica leaves contain diverse secondary metabolites with notable antibacterial potential, yet their effects on Streptococcus pneumoniae and Streptococcus pyogenes remain insufficiently characterised. This study evaluated the antibacterial activity of ethanol extract from A. indica leaves using an integrated computational and experimental approach. Computational screening identified 35 bioactive compounds retrieved from the literature and public databases. Molecular docking revealed strong binding affinities of Chrysin, epicatechin, and ellagic acid toward Pneumolysin (7TXL), and Nimbaflavone, quercitrin, and Chrysin (8DOV). In vitro percentage-kill assays demonstrated bactericidal activity, achieving >98% killing of S. pneumoniae and >99% of S. pyogenes within 5 min. These findings confirm the potential antibacterial activity of A. indica leaf extract. The combined computational and experimental evidence suggests that its known bioactive may contribute to alternative strategies for pneumonia management amid escalating antibiotic resistance.