Aim To investigate the changes of plasma miR-765 level and its target gene function in patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM), and to explore the clinical significance of plasma miR-765 as a potential biomarker of CHD combined with T2DM. Methods 56 patients with CHD diagnosed by coronary angiography were collected. According to whether T2DM was combined or not, the patients were divided into two groups:simple CHD group (CHD group, 33 cases), CHD combined with T2DM group (CHD＋T2DM group, 23 cases).Another 30 cases with negative results of coronary angiography were selected as control group. Gensini scoring system was used to evaluate the degree of coronary artery stenosis. Plasma miR-765 levels were detected by quantitative real-time PCR. Bioinformatics analysis was used to predict the target genes of miR-765, and target genes Gene Ontology (GO) function annotation and coding protein-protein interaction (PPI) network construction were carried out. Results Compared with the CHD group, Gensini score was significantly higher in the CHD＋T2DM group. Compared with the control group, the plasma miR-765 level of CHD group was significantly higher (P＜0.05); compared with the CHD group, the plasma miR-765 level of CHD＋T2DM group was significantly higher (P＜0.05). A total of 30 potential target genes were obtained by bioinformatics analysis of target genes. The results of classification analysis of biological function, molecular function and cell composition showed that miR-765 was involved in the regulation of cell morphogenesis and chemotaxis, inflammation, immunity, homeostasis and transport, and protein amino acid phosphorylation, suggesting that miR-765 might regulate chemokine signaling pathway, calcium signaling pathway and phosphatidylinositol signaling pathway. Further PPI network analysis showed that there were complex interactions among the proteins encoded by miR-765 target gene. Conclusion Plasma miR-765 level is significantly increased in CHD patients with T2DM. Plasma miR-765 is a potential clinical diagnostic biomarker in CHD patients with T2DM, which has high diagnostic value for CHD combined with T2DM.