Squid, as a very important economic marine species, accounts for 5 % of the total catch of fish and cephalopods. The waste from the processing process of squid can be used for collagen extraction, which has great application value in the field of biomedical materials. Here, we obtained squid cartilage gelatin (SCG) with different molecular weights by adjusti.ng the reaction conditions and used for the treatment of chronic wounds in diabetes. SCG extracted at low temperatures and short heating times demonstrated a more intact structure, higher molecular weight, and superior gel stability. Based on cell study and transcriptome analysis, SCG with high molecular weight significantly promoted cell adhesion, because it provided more contact sites for cells, whereas small molecules of SCG could directly reduce inflammation. Animal studies have demonstrated that SCG significantly promotes diabetic wound healing as evidenced by reducing inflammation, inducing vascular regeneration, promoting tissue growth, re-epithelialization, collagen deposition and remodeling. This study elucidated the immunoregulatory mechanisms of SCG with different molecular weights, and validated its potential application in chronic wound healing in diabetes.