In this study, we demonstrated that inhibition of Drp1 hyperactivation using P110, a selective peptide inhibitor of Drp1/Fis1 interaction that we developed, reduced pathological mitochondrial fission in ALS using several ALS patient‐derived fibroblasts, motor neurons expressing G93A mutation, and a SOD1G93A mouse model. Here, FIS1 is linked to amyotrophic lateral sclerosis.