Introduction: This study aimed to evaluate the efficacy of Pluchea dioscoridis leaf extract on growth, survival, morphogenesis, and virulence gene expression of Candida albicans. Methodology: Anticandidal activity was studied using the hole-plate method against four pathogenic C. albicans strains from clinical isolates. The effect of the extract on the growth profile of the yeast was also examined via a time-kill assay. Microscopic observations using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were made to determine the major alterations in the microstructure of C. albicans. Quantitative changes in phospholipase, hemolysin, and secreted aspartyl proteinase (SAP1 and SAP10) genes expression as virulence factors were analyzed using real-time polymerase chain reaction (RT-PCR). Results: The extract exhibited high anticandidal activity, with the zones of inhibition between 0.5 and 6 cm, and recorded a minimum inhibitory concentration (MIC) value of 30 mg/mL. The time-kill study suggested that the extract possessed yeasticidal properties at higher concentrations and eradicated the growth of yeast cells. The SEM and TEM micrographs exhibited major abnormalities that occurred on the yeast cells after being exposed to the extract, resulting in complete alterations in their morphology and collapse of the cells beyond repair. At MIC concentration, phospholipase, proteinase, and hemolysin gene expression was reduced to 90%, 70%, 90% for SAP1, and 40% for SAP10,respectively, compared to that obtained from untreated C. albicans, as demonstrated by quantitative reverse transcription (RT)-PCR analysis. Conclusions: The P. dioscoridis leaf extract may be an effective anticandidal agent to treat pathogenic yeast infections.