Disease-modifying therapies can modulate the intestinal barrier. Different disease-modifying therapies in clinical use may beneficially modulate intestinal barrier function through a variety of mechanisms. (1) Oral disease-modifying therapies have antimicrobial properties, while minocycline is a tetracycline antibiotic. Dimethyl fumarate acts as a Michael acceptor and can deplete bacterial nucleophilic thiols. (2) Glatiramer acetate has been shown to increase syndecan, the most abundant heparan sulphate proteoglycan in the gastrointestinal tract. (3) Fingolimod, dimethyl fumarate and minocycline increase tight junction expression. Dimethyl fumarate increases zona occludens-1 (ZO-1) in a heme-oxygenase-1 (HO-1) dependent pathway, while S1P signalling increases E-cadherin (E-CN). (4) Most disease-modifying therapies modulate lymphocyte (LYM) populations and functions in non-neurological tissues, such as in the lamina propria. Whether any of these effects have a mechanistic relevance for their therapeutic action is unknown.