Streptococcus pneumoniae is a leading cause of bacterial pneumonia. The continuing global threat of antimicrobial resistance alongside pneumonia being one of the largest infectious diseases worldwide raises the urgent need of novel alternatives to antibiotics using molecular docking, and Citrus flavonoids are well-known antibacterial agents. Purpose: In-silico and in-vitro evaluation of the antibacterial activity of 29 flavonoid found Citrus peels to identify their activity against S. pneumoniae isolated from pneumonia patients and a reference strain. Methods: Conventional methods had been used to identify Streptococcus pneumoniae and determine its sensitivity to antibiotics. Well diffusion and microdilution methods were employed for the in-vitro evaluation. The in-silico study was done using two docking programs as modern approaches to identify activity to Toxin-Antitoxin complex (HicBA) as a possible target in S. pneumoniae. Results: Binding affinity using iGEMDOCK was lower for glycosidic flavonoids than their respective aglycones. Binding affinity using AutoDock Vina for Quercetin (-6.7 kcal/mole), Rutin (-7.1 kcal/mole) compared to Vancomycin (-6.4 kcal/mole), minimum inhibitory concentration (MIC) range of the of 62.5-500 µg/ml compared to Rutin (-78->500 µg/ml). Conclusions: The docking study implied that HicBA may be a potential target for Citrus flavonoids. Rutin had milder effects on S. pneumoniae denoting that sugar moiety's role is limited. Quercetin may be a possible antibacterial agent for S. pneumoniae.