INTRODUCTION: Cognitive impairment is common and debilitating among persons with multiple sclerosis (MS) and might be managed with exercise training. However, the effects of exercise training on viscoelastic brain properties in this population are unknown. The present pilot study adopted a single-blind randomized controlled trial (RCT) design and is the first to examine the effect of an aerobic exercise training intervention on learning and memory and hippocampal viscoelasticity using magnetic resonance elastography (MRE) in persons with MS. METHODS: Eight fully ambulatory females with MS were randomly assigned into exercise training intervention or waitlist control conditions. The intervention condition involved 12 weeks of supervised, progressive treadmill walking exercise training. All participants underwent measures of learning and memory (i.e., California Verbal Learning Test-II; CVLT-II) and further underwent MRE scans for measurement of shear stiffness (μ) and damping ratio (ξ) of the hippocampus before and after the 12-week period. RESULTS: Overall, there were small-to-moderate intervention effects on CVLT-II performance (d = 0.34) and large intervention effects on hippocampal μ (d = 0.94) and hippocampal ξ (d = -1.20). Change in CVLT-II scores was strongly associated with change in μ (r = 0.93, p < 0.01) and ξ (r = -.96, p < 0.01) of the hippocampus. CONCLUSION: This small pilot RCT provides exciting proof-of-concept data supporting progressive treadmill walking exercise training for potentially improving learning and memory and underlying hippocampal viscoelastic properties in persons with MS. This is important given the high prevalence and burden of MS-related memory impairment.