Duchenne Muscular Dystrophy (DMD) is a severe muscle-wasting disease brought about by a genetic mutation that prevents the synthesis of dystrophin, a protein necessary for myofiber cell membrane integrity. There is no known method capable of curing DMD, although therapeutic strategies have been developed to temporally delay its progression. One potential strategy involves bottlebrush polymers, synthetic copolymers comprising side chains branching from repeating units of a linear polymer backbone to create a “bottlebrush”-like structure. Our study sought to elucidate the effects of these copolymers and their dosages on dystrophin-deficient skeletal myofiber contractility, thereby determining their efficacy at stabilizing the muscle sarcolemma in DMD. We conducted in vitro functional assays of myofibers from flexor digitorum brevis (FDB) muscles harvested from adult mdx mice. Peak contraction height (the maximum length decreased during contraction), among other parameters, was analyzed in muscle cells before and after treatment with a certain variation and concentration of bottlebrush copolymer. We used paired t-tests to determine statistical significance. Following treatment with a 100 nM dose of burgundy bottlebrush (BB; B-PEO(10,40)-s-PPO(15,7)) copolymers, myofibers demonstrated a statistically significant increase in peak contraction height compared to pre-treatment values. Cyan bottlebrush (CB; B-PEO(10,40)-PPO(15,7)) copolymers conferred a similar increase in contractile ability after a 100 nM dose and, to a lesser extent, a 10 nM dose. We found no contractility improvement in myofibers treated with 10 nM BB or 1 nM CB. These results indicate that both bottlebrush copolymers are effective at stabilizing mdx myofibers in vitro. If these potent results translate to in vivo biology, they hold promise for advancing synthetic membrane stabilizers as a novel therapy for DMD.