Functional plasticity has been demonstrated in multiple sclerosis (MS) studies. However, the intrinsic brain activity complexity alterations remain unclear. Here, using a coarse-graining time-series procedure algorithm, we obtained multiscale entropy (MSE) from a retrospective multi-centre dataset (208 relapsing-remitting MS patients and 228 healthy controls). By linear mixed model analysis, we demonstrated (1) increased entropy at scale 1 and decreased entropy at scale 6, indicating that regional brain activity shifted towards randomness in the stable MS subgroups (n = 159), and (2) decreased entropy across scales 1-6, trending towards regularity in the acute MS subgroups (n = 49). The main results of the correlation analysis included the following: (1) Decreased entropy was associated with lesion volume and brain volume specifically on longer time scales (scale 3-5), and (2) increased entropy of scale 3 was associated with clinical disability scores. These findings reflect the critical role of structural disruption in the brain activity complexity of BOLD signals in MS patients.