A majority of the existing magnetodielectric (MD) effects based on spin-lattice coupling or magnetic transitions are either too weak or far below room temperature, which challenges the potential applications of MD materials. Here, a giant room-temperature MD coefficient of −62% at 1 Tesla (T) in disordered rutile NiNb 2 O 6 (r-NiNb 2 O 6 ) ceramic in terms of the spin-dependent polaron hopping is demonstrated. The r-NiNb 2 O 6 exhibits a near-room-temperature dielectric relaxation, which is ascribed to the polaron-hopping-induced grain polarization. This dielectric relaxation process, strikingly, can be controlled by the external magnetic field (H = 1 T) at 220 K< T< 310 K, achieving a giant MD coefficient of −62% (at 10k Hz) at 298 K. Further systematic investigations on the magnetic, electrical, and magnetoelectric coupling properties attribute the MD effect in r-NiNb 2 O 6 to a pure response of the spin-dependent polaron hopping to applied magnetic field. This clearly reveals that the MD effect is subject to a competition among the polaron hopping activation, spin-lattice coupling, and spin thermal fluctuation.