Muscular dystrophies are a heterogeneous group of genetic diseases involving mutations in genes that compromise sarcolemma stability, muscle strength, and repair. Limb-girdle muscular dystrophy type 2B (LGMD2B) is a type of dysferlinopathy caused by mutations in encoding of the dysferlin protein and is characterized by the following: diminished membrane repair, delayed removal of necrotic muscle fibers, loss of calcium sensitivity leading to signaling mis-regulation, muscle atrophy, malformation of transverse tubule structure and increased inflammatory infiltrate. LGMD2B has an incidence of 1/100,000-1/200,000 depending on geographic location and ethnic background. The lack of a cure and treatment options for LGMD2B patients requires increased research to develop therapeutics to decrease disease progression. Galectin-1 (Gal-1) is a small 14.5 kDa protein with a carbohydrate recognition domain capable of stabilizing the sarcolemma by increasing levels of ECM proteins. Gal-1 has been proven to improve muscle repair capacity in Duchenne muscular dystrophy (DMD) models by increasing extracellular interaction resulted in healthier muscle fibers. Our hypothesis is that Gal-1 increases membrane repair capacity and myogenic potential of dysferlin-deficient muscle cells and muscle fibers. We used recombinant human galectin-1 (rHsGal-1) to treat dysferlin-deficient models. We found that rHsGal-1 treatment for a 48 – 72 h period promotes myogenic maturation with enhancements in size, myotube alignment, and membrane repair capacity in both dysferlin-deficient myotubes and myofibers. Additionally, we discovered that the carbohydrate recognition domain of Gal-1 is necessary for observed membrane repair. Furthermore, membrane repair with rHsGal-1 treatment in dysferlin-deficient and wild-type myotubes and myofibers was calcium-independent. Similarly, one-month in vivo treatment with rHsGal-1 revealed significant improvement in membrane repair capability. Together, our results reveal Gal-1 mediates membrane repair capacity in dysferlin deficient models and increases markers for myogenesis, thus indicting an efficacy in using Gal-1 as a new protein treatment in LGMD2B.