The chemical composition and thermal property of cuttlefish (Sepia pharaonis) muscle were studied. The head and mantle contained 11.9-14.9% protein, 0.5% fat, 1.2-1.3% ash, and 0.6-1.8% collagen. Lipids from the head and mantle contained phospholipid as the major component (78.6-87.8% of total lipid), with 10.6-19.5% diglyceride. Polyunsaturated fatty acids constituted 50.3-54.9% of fatty acids with a high content of DHA and EPA. The n-3 PUFA contents were greater than n-6 PUFA. The C16:0 and C18:0 were the most abundant saturated fatty acid in the head and mantle. The cuttlefish muscle consisted of myofibrillar proteins as the major protein (53.1-58.4%). Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that myosin heavy chain (MHC), paramyosin and actin were the major proteins and varied with the portions. Differential scanning colorimetric (DSC) study revealed three transitions corresponding to the thermal denaturation of myosin and paramyosin, connective tissues and actin, at temperatures of 49.8-50.3, 59.8-60.3 and 74.7-78.8 °C, respectively. Zinc and iron were the dominant trace minerals in both portions.