Objective: To determine the major changes in the microstructure of Candida albicans (C. albicans) after treatment with Euphorbia hirta (E. hirta) L. leaf extract. Methods: Transmission electron microscopy was used to study the ultrastructural changes caused by E. hirta extract on C.albicans cells at various exposure time. Results: It was found that the main abnormalities were the alterations in morphology, lysis and complete collapse of the yeast cells after 36 h of exposure to the extract. Whereas the control cultures showed a typical morphology of Candida with a uniform central density, typically structured nucleus, and a cytoplasm with several elements of endomembrane system and enveloped by a regular, intact cell wall. Conclusions: The significant antifungal activity shown by this methanol extract of E. hirta L. suggests its potential against infections caused by C. albicans. The extract may be developed as an anticandidal agent.