FUNGAL infections due to fluconazole-resistant Candida albicans are a serious clinical problem, requiring new efficient antifungal treatment. The present study evaluated the susceptibility of fluconazole-resistant C. albicans to green silver nanoparticles. A total of 40 isolates were examined for the expressions of CDR1, CDR2, and MDR1 gene by quantitative reverse transcription polymerase chain reaction. The antifungal activities of green silver nanoparticles alone and/or in combination with fluconazole (to improve antifungal activity) were assessed by broth microdilution assay and transmission electron microscopy. The effect of fluconazole and/or green silver nanoparticles on the production of C. albicans to protease and phospholipase was also evaluated. And finally, animal model was used to prove the safe and effective use of green silver nanoparticles in the treatment of fluconazole-resistant C. albicans. For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and green silver nanoparticles were 64 and 4.84 μg/ml, respectively. Green silver nanoparticles decrease the production of protease and phospholipase enzymes. The expression of both CDR1 and CDR2 were decreased after exposure to green silver nanoparticles, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and green silver nanoparticles were used. Green silver nanoparticles may be causing suppression of the CDR1, CDR2 and MDR1 expression in fluconazole-resistant C. albicans. The results suggest the use of green silver nanoparticles as a safe and effective treatment against fluconazole-resistant C. albicans.