We found a large and unique magnetoresistance (MR) effect for CaMn2Bi2. When the magnetic field was applied along the crystallographic c axis at low temperatures, the resistivity increased with the magnetic field and the MR ratio reached several hundred percent, but then it decreased with further increasing the applied field. In addition, the angle dependence measurement revealed a strong anisotropy. This compound is an antiferromagnetic semiconductor with a narrow band gap, and Mn atoms form a corrugated honeycomb lattice. Therefore, a frustration among the magnetic moments is expected, and we propose that our observations can be understood by a nonmonotonic modulation of magnetic fluctuation under the magnetic field.