Research on the novel technology of reductive leaching manganese from low-grade pyrolusite using biogas residual as reductant has been conducted. According to the response surface design and the analysis of results, orthogonal experiments have been conducted on the major factors and effects of the factors on the manganese leaching efficiency have been studied. The maximum manganese leaching efficiency could be optimized to nearly 100%, when the mass ratio of biogas residual to pyrolusite was 0.19:1, the volume-to-mass ratio of sulfuric acid to pyrolusite was 8: 1, the sulfuric acid concentration was 25%, and the reaction time was 2.5 h. The results of the manganese leaching efficiency of the actual experiments were close to those of the fitting model by the verification experiments, indicating that the optimum solution has a relatively high reliability. Other low-grade pyrolusite, such as Guangxi pyrolusite (China), Hunan pyrolusite (China), and Guizhou pyrolusite (China), were tested and all these materials responded well giving nearly 100% manganese leaching efficiency.