Diabetic cardiomyopathy (DbCM) is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism plays a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise role of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. This study found that TGR5 deletion in cardiomyocytes increased myocardial lipid accumulation and cardiac dysfunction in mice subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic *db/db* genetic background. Mechanistically, TGR5 deletion promoted CD36 palmitoylation and membrane localization through the palmitoyl acyltransferase DHHC4. The findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, highlighting the therapeutic potential of targeting TGR5 in managing DbCM.Diabetic cardiomyopathy (DbCM) is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism plays a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise role of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. This study found that TGR5 deletion in cardiomyocytes increased myocardial lipid accumulation and cardiac dysfunction in mice subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic *db/db* genetic background. Mechanistically, TGR5 deletion promoted CD36 palmitoylation and membrane localization through the palmitoyl acyltransferase DHHC4. The findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, highlighting the therapeutic potential of targeting TGR5 in managing DbCM.