The electronic spin of nitrogen-vacancy (NV) centers in diamond is extremely sensitive to local magnetic fields, which makes them a valuable tool for sensing nuclear and electronic spins in their vicinity. While the detected spin targets are static in most applications, the situation is entirely different for ambient thermal conditions as encountered, for example, in biological environments. In this case, the spin-carrying molecules and thus the spins undergo random diffusive motion. In our work we simulate the motion of diffusive spins for specific molecules and derive effective models for the interaction between NV centers and spin targets. We find in particular that spins undergoing rapid diffusion in a restricted domain behave as “averaged” spins, which can still be detected under realistic experimental conditions.