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The increasing frequency of antifungal drug resistance among pathogenic yeast “<i>Candida</i>” has posed an immense global threat to the public healthcare sector. The most notable species of <i>Candida</i> causing most fungal infections is <i>Candida albicans.</i> Furthermore, recent research has revealed that transition and noble metal combinations can have synergistic antimicrobial effects. Therefore, a one-pot seedless biogenic synthesis of Ag-Ni bimetallic nanoparticles (Ag-Ni NPs) using <i>Salvia officinalis</i> aqueous leaf extract is described. Various techniques, such as UV–vis, FTIR, XRD, SEM, EDX, and TGA, were used to validate the production of Ag-Ni NPs. The antifungal susceptibility of Ag-Ni NPs alone and in combination with fluconazole (FLZ) was tested against FLZ-resistant <i>C. albicans</i> isolate. Furthermore, the impacts of these NPs on membrane integrity, drug efflux pumps, and biofilms formation were evaluated. The MIC (1.56 μg/mL) and MFC (3.12 μg/mL) results indicated potent antifungal activity of Ag-Ni NPs against FLZ-resistant <i>C. albicans</i>. Upon combination, synergistic interaction was observed between Ag-Ni NPs and FLZ against <i>C. albicans</i> 5112 with a fractional inhibitory concentration index (FICI) value of 0.31. In-depth studies revealed that Ag-Ni NPs at higher concentrations (3.12 μg/mL) have anti-biofilm properties and disrupt membrane integrity, as demonstrated by scanning electron microscopy results. In comparison, morphological transition was halted at lower concentrations (0.78 μg/mL). From the results of efflux pump assay using rhodamine 6G (R6G), it was evident that Ag-Ni NPs blocks the efflux pumps in the FLZ-resistant <i>C. albicans</i> 5112. Targeting biofilms and efflux pumps using novel drugs will be an alternate approach for combatting the threat of multi-drug resistant (MDR) stains of <i>C. albicans</i>. Therefore, this study supports the usage of Ag-Ni NPs to avert infections caused by drug resistant strains of <i>C. albicans</i>.