A highly efficient destruction of bisphenol A (BPA) was explored through Mn2+-mediated activation of periodate under ambient conditions. The conjunction of periodate with different transition metals was investigated, and Mn exhibited the best catalytic performance. The periodate oxidation of BPA could be rapidly proceeded loading with low amount of Mn2+ and in a wide pH range. The presence of humic acid significantly enhance the degradation efficiency due to its electron transfer characteristic. Besides, molecular oxygen played an indispensable role during the reaction, and superoxide radicals was discriminated as the leading reactive species for BPA degradation. The homogeneous periodate activation initiated by Mn2+ provides a feasible approach for the degradation of organic contaminants without external energy.