Propolis, a natural antibiotic, which is in high demand in dentistry is a resinous substance. The main ingredient of propolis that is required for antibiotic effect is flavonoids and phenolic acids. Although propolis is a promising option for the control of oral microbes with lower related hazards and a good immunomodulator effect, its composition differs considerably depending on its botanical origin, the site and the season of collection. This original research aims to find the chemical composition and minimum inhibitory concentration (MIC) of propolis procured from different places of Karnataka state. The results would help the dentist and the pharmacist to select the best propolis to use as antibiotics in treating oral disease. Propolis sample from 5 different locations of Karnataka was procured from single apiary in Bangalore. Extraction of propolis using two different extracting solvents was carried out. The total phenolic content, total flavonoid content and MIC of each sample were analyzed. Water extract propolis of Sullia and Hubli was highly active against tested organism with the MIC <0.312; alcohol extract of Sullia, Hubli and Chitradurga was moderately active with the MIC between 0.312 and 5 mg/ml. Vijayapura and Bagalkot were least active with the MIC >5 mg/ml at tested concentration. Propolis procured from different locations of Karnataka can be used as an antimicrobial agent with varying concentrations. However, when propolis is procured for therapeutic purpose, then it needs to be tested for its chemical composition before being utilized.