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<div>The effects of three chemical compounds, known to have anti-microbial activities, were examined against <i>Ralstonia solanacearum</i> (Rs). The compounds were 3-indolyacetonitrile (IAN), p-benzoquinone (pBQ), and 6,7-dihydroxycoumarin (6-7-D). The minimal inhibition concentration against Rs was 640μM, 25μM, and 125μM for IAN, pBQ and 6-7-D, respectively. Sub-inhibitory concentrations, 160μM for IAN, 12.5μM for pBQ, and 50μM for 6-7-D, were used to determine bacterial growth rates. IAN was significantly more effective in inhibiting growth compared to pBQ and 6-7-D. Fluorescent microscopy with GFP-labeled W7 strain demonstrated that IAN limited bacterial colonization of plant roots the most. Tobacco cultivars K326 and Speight168 were treated with the compounds 48-hours before, at the same time or 48-hours after inoculation. IAN was the most effective compound in limiting disease and treating at inoculation suppressed the disease the most regardless of the compound. Quantitative real-time PCR revealed that pBQ significantly inhibited the expression of the three pathogenicity-related genes, <i>phcA</i>,<i> xpsR</i>,<i> and pehR</i>, compared to the untreated control whereas 6-7-D did not have any significant effect. With IAN, expression of <i>phcA</i> and <i>xpsR</i> was repressed, but the expression of <i>pehR</i> was increased. Understanding the unique Rs physiological traits and their responses to stimuli may provide insights for future phytobiome research.</div>