Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We propose the use of g-ratio–based connectome for evaluating the network topology of MS since it is reported to be useful in the evaluation of demyelinating lesions in MS. Here, we evaluated the structural connectome of patients with MS, as mapped by MR g-ratio based connectome. The network-based statistic identified a subnetwork of reduced connectivity in patients with MS involving the limbic area. In conclusion, MR g-ratio–based connectome analysis can potentially detect changes in brain topology in MS with high sensitivity.