Candida albicans is considered as an opportunistic yeast fungus that is considered as the principal reason of dangerous invasive infections with high death rates. In this research, we were the first to mycosynthesize silver nanoparticles (AgNPs) from the rhizospheric fungus Penicillium griseofulvum (PG) cell-free filtrate (CFF) and examined their antifungal effectiveness alone or in combination with the antifungal Amphotericin B (PG-AgNPs/AMB) against C. albicans. A total of 155 fungal isolates, which were recovered from the rhizosphere soil of Reseda pentagyna, belonged to fifteen species represented by five different genera. PG-AgNPs were characterized by transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX), zeta potential, X-ray diffraction (XRD), UV-Vis spectroscopy, and Fourier transform infrared spectroscopy (FTIR). The disc diffusion assay presented the anti-candidal activity of PG-AgNPs against C. albicans with a minimum inhibitory concentration (MIC) of 16 µg/mL. Additionally, PG-AgNPs/AMB (16/32 μg/mL) exhibited a potent synergistic antifungal activity with an inhibition zone of 27 mm. PG-AgNPs/AMB (16/32 μg/mL) completely inhibited morphogenesis and repressed the adherence and biofilm establishment of C. albicans by 91% and 87%, respectively. Interestingly, PG-AgNPs/AMB suppressed the antioxidant-related enzymes in C. albicans by more than 80%. PG-AgNPs/AMB displayed cytoplasm degeneration and damage of cell wall as examined by scanning and transmission electron microscopy. Remarkably, PG-AgNPs did not show any signs of cytotoxicity on either primary mesenchymal stem cells or human gingival fibroblast cell line HGF-1. In conclusion, we identified PG-AgNPs/AMB as an innovative therapeutic candidate for the treatment of candidiasis.