Cdk5 regulatory associated protein 1-like 1 () is one of the most reliable risk genes for type 2 diabetes mellitus (T2DM). Because controls glucose-induced insulin secretion by K channel responsiveness and faithful decoding of Lys codons to prevent mistranslation in pancreatic β-cells, a rescuer of defects is expected as a new antidiabetes drug. We found that eperisone analogs effectively rescued mistranslation in a -deficient dual-luciferase reporter gene system ( is a prokaryotic homologue of eukaryotic ). Among them, compounds and demonstrated significant antihyperglycemic efficacy in an oral glucose tolerance test by subcutaneous administration in Wister rats, along with a significant enhancement of insulin secretion in the MIN6 insulinoma cell line without cytotoxicity. These results indicate that could be a viable molecular target for a new anti-T2DM medication.