Aim To identify the active compounds from the Streptomyces sp. MJM4426 that can protect rice from bacterial blight disease (BB), and to evaluate the potential of this Streptomyces strains and the compound for biocontrol of rice bacterial blight disease. Methods and Results The ethyl acetate extract of Streptomyces sp. MJM4426 can significantly protect rice leaf explants from the infection of Xanthomonas oryzae pv. oryzaeKACC 10331 (Xoo), the pathogen which cause BB. To identify the active compounds, the ethyl acetate extract of Streptomyces sp. MJM4426 was fractionated through a Sephadex LH‐20 column chromatography, and further purified by preparative HPLC guided by the inhibitory activity against BB in rice leaf explants. UPLC‐Q‐TOF/MS analysis showed the active compound displayed its m/z values at M+H+ 467·2086 and M+FA−H− 511·1963, and the molecular formula was estimated as C28H26N4O3 which is identical to commercial standard staurosporine. In this study, the isolated staurosporine dramatically suppressed bacterial blight in rice leaf explants with the lowest concentration at 12·5 μmol l−1, however, it exhibited low inhibitory activity against Xoo with the MIC value at 256 μg ml−1. In addition, greenhouse study showed both crude extract and purified staurosporine can suppress the bacterial blight at the concentration of 5000 and 200 μg ml−1 respectively. Conclusion Streptomyces sp. MJM4426 can protect rice leaf explants from the infection of Xoo by producing staurosporine, but not by direct inhibitory activity against Xoo. Significance and Impact of the Study This is the first report that staurosporine can protect rice leaf against bacterial blight disease and showed the potential of Streptomyces sp. MJM4426 as an alternative to chemical bactericide for bacterial blight disease in rice.