Overall, our study for the first‐time demonstrated that (a) stroke causes muscle atrophy, in part, through the SirT1/PARP‐1/ZNF216 signaling mechanism; (b) SirT1 can block muscle atrophy in response to different types of atrophic signals via different signaling mechanisms; and (c) SirT1 is a critical regulator of post‐stroke muscle mass. Here, SIRT1 is linked to stroke disorder.