Global increase in the level of antimicrobial resistance among bacterial pathogens has prompted the search for alternative treatment from medicinal plants. Phyllantus muellerianus leaves has been used traditionally against microorganisms of medical importance, hence the need to evaluate the pharmacological pathways and mode of actions using in vitro and in silico approaches. Clinical isolates of eight (8) microorganisms associated with urinary tract infections were obtained and identified using morphological and biochemical methods. Phyllantus muellerianus leaves were extracted and purified by solvent partitioning. Ethyl acetate fraction of PM had the highest yield and zone diameter range from 13.5 ± 1.00 to 28 ± 1.53 mm. The rate of protein leakage per time interval of Staphylococcus aureus increased from 9.29 μg/ml at 0 min to 17.43 μg/ml at 120 min while leakage in Candida albicans also increased from 8.57 μg/ml at 0 min to 70.43 μg/ml at 120 min. GCMS fingerprints, pharmacodynamics and pharmacokinetic studies revealed the active agent as quindoline, an azaindole and isotere of indoles having a binding energy of −9.1 kcal/mol. Analyses of the structural and atomic orientations of quindoline, and superimposition on ciprofloxacin, a common antibiotic revealed an interesting comparison, effecting a stronger binding affinity of Quindoline-HMG-CoA complex.