Aims: This study aimed to evaluate the effectiveness of four Psidium guajava leaf extracts against three strains of Candida albicans and a strain of Cryptococcus neoformans. Study Design: Experiment-observational study. Place and Duration of Study: P. guajava leaves were collected from specific areas in Regions Three and Four in Guyana; and the preparation of the leaf extracts and the treatment against the fungi were performed in two laboratories at the University of Guyana from August 2022-September 2023. Methodology: P. guajava leaves were washed with water, air-dried at room temperature, and ground in a disinfected food mixer. Extracts were prepared by soaking the ground leaves in different solvents, and then using the rotary evaporator to reduce the solutions and obtain crude extracts. Filter paper discs were prepared and allowed to soak in various concentrations of the crude extracts. The discs were then subjected to antifungal susceptibility testing on Potato Dextrose agar seeded with an appropriate fungus according to Clinical Laboratory Standards Institutes guidelines. The plates were incubated and the zone of inhibition (ZOIs) was measured. Results: P. guajava leaves were effective against all four strains of fungi evaluated. The largest ZOI was observed for C. neoformans (25 mm) with the ethyl acetate extract at 100 mg/mL concentration. Large ZOI was also observed for the three strains of C. albicans (10-15 mm). For one of the C. albicans strains, a ZOI significantly higher than the antifungal agents (ketoconazole and fluconazole) was observed with the P. guajava ethyl acetate extract at 100 mg/mL. Conclusion: It can be concluded that P. guajava leaves have antifungal activity against C. albicans and C. neoformans, potentially greater than current antifungal agents like ketoconazole and fluconazole.