Combination antimicrobial therapy (CAT) involves intentional addition of two or more antimicrobial agents for better therapeutic outcome. CAT is normally applied for treatment of polymicrobial infections, life-threatening infections and prevention of the emergence of resistance. This research aimed at determining the combined activity of blue vitriol, brimstone and black stone on clinical Candida species isolates using Fractional Inhibitory Concentration Index. The brimstone, blue vitriol and black stone samples were purchased from a community market in southeastern Nigeria. The isolates were obtained from high vaginal swab samples of patients attending a Teaching hospital in Nigeria and identified based on their morphological, physiological and molecular characteristics. The minimal inhibitory concentrations (MIC) of the samples were determined using the broth dilution method. The fractional inhibitory concentration indexes (FICI) of the samples against the isolates were obtained from their individual FIC values. FICI of <1 indicates synergism; 1 to 2 (Indifference); while >2 (antagonism). All the test agents were synergistic against C. albicans (FICI < 1). All the test agents were indifferent against C. tropicalis (FICI 1 - 2). Brimstone + black stone combination was indifferent (FICI 1 - 2) against C. glabrata; while all the test agents were antagonistic against the isolate (FICI > 2). Blue vitriol + Black stone combination was antagonistic (FICI > 2) against C. parapsilosis; Blue vitriol + brimstone was indifferent (FICI 1 - 2); while brimstone + black stone was synergistic (FICI < 1). The findings have revealed that antimicrobial combination outcome could be synergistic, antagonistic or indifferent; thus the need for proper in vitro screening before combination therapy.