Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy (DCM). Methods The technology platform of Chinese medicine system pharmacology (TCMSP) and the small molecule drug target prediction (Swiss Target Prediction) platform were used to excavate the active components of Scutellariae Radix and the target of its response. DCM related disease gene targets were screened using GeneCards, Disgene, UniPort and OMIM databases, and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram. Cytoscape 3.9.1 software was adopted to visualize the key target network. Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM, and draw pathway maps through the KEGG database. H9c2 and AC16 cardiomyocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group, 35 mmol/L D-glucose as the high glucose group, and 10 μmol/L Baicalin was used for intervention. The levels of TGF-β1, collagen Ⅰ (COLⅠ) and collagenⅢ (COLⅢ) mRNA were detected by RT-qPCR, and the expression of Smad2/3, p-Smad2/3, COLⅠ and COLⅢ protein were detected by Western blot, TGF-β1 level in supernatant was assessed by ELISA. Results Through the above platform, a total of 33 effective ingredients including Baicalin, 441 core targets, and 1 884 DCM disease genes were retrieved, 150 core genes for treating DCM with Scutellariae Radix were obtained. The drug-disease interacted genes such as TGF-β1, TP53, MMP-9 and IL-6 were obtained through String PPI, KEGG signaling pathways such as MAPK and PI3K/Akt were enriched. In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1, COLⅠ and COLⅢ mRNA levels, p-Smad2/3, COLⅠ and COLⅢ protein levels, and significantly increased the content of TGF-β1 in the supernatant, while Baicalin weakened its expression. Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets, among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.