Limb-girdle muscular dystrophy type 2B (LGMD2B) is caused by mutations in the dysferlin gene, resulting in non-functional dysferlin, a key protein found in muscle membrane. Treatment options available for patients are chiefly palliative in nature and focus on maintaining ambulation. Our hypothesis is that galectin-1 (Gal-1), a soluble carbohydrate binding protein, increases membrane repair capacity, myogenic potential, M2 macrophage polarization and decreases NF-κB inflammation in dysferlin-deficient models. To test this hypothesis, we used recombinant human galectin-1 (rHsGal-1) to treat dysferlin-deficient models. We show that rHsGal-1 treatments of 48 h-72 h promotes myogenic maturation as indicated through improvements in size, myotube alignment, and myoblast migration in dysferlin-deficient myotubes. Furthermore, rHsGal-1 showed an increased membrane repair capacity of dysferlin-deficient myotubes. Improvements in membrane repair after only a 10 min rHsGal-1treatment suggests mechanical stabilization of the membrane due to interaction with glycosylated membrane bound, ECM or yet to be identified ligands through the CDR domain of Gal-1. rHsGal-l significantly reduces canonical NF-κB inflammation through TAK 1, P65, P50. Lastly we find 2.7 mg/kg in vivo rHsGal-1 treatment in BLA/J mice supports an M2 cyto-regenerative macrophage populations. Together our novel results reveal Gal-1 remediates disease pathologies in LGMD2B through changes in integral myogenic protein expression, mechanical membrane stabilization, immune modulation, and reducing canonical NF-κB inflammation.