Natural compounds are organic products synthesized by living organisms or found in nature. The natural compounds of interest were blue vitriol and brimstone. Caries is a chronic, multifactorial disease, which causes destruction and demineralization of hard tissues of teeth by acid production occurring from bacterial fermentation of food. The antimicrobial activity of brimstones and blue vitriol (blue stone) against isolates from dental caries was evaluated. Eighty-five dental swab specimens were aseptically collected from dental caries patients. The isolates were identified based on their microscopic, macroscopic, biochemical and molecular characteristics. They include Candida tropicalis, Streptococcus mutans, Lactobacillus sppand Staphylococcus aureus. Agar-well diffusion and broth dilution methods were used to determine the antimicrobial susceptibility of the isolates. The test showed that the isolates were susceptible to some of the natural stones as zones of inhibition were observed. Blue stone gave the highest inhibition zone diameter of 46.20±1.10 mm against Lactobacillus spp at 200 mg/ml. Brimstones showed no zone of inhibition on all the isolates. The Minimal Inhibition Concentration of bluestone was 50 mg/ml; and 200 mg/ml for brimstone against Staphylococcus aureus. The minimum bactericidal concentration of bluestone was 50 mg/ml against Staphylococcus aureus and 200 mg/ml against the other isolates. Thus, natural stones can be used as antimicrobials in the production of dental care products and in treatment of dental caries.