The myokine irisin and the adipokine leptin are key humoral mediators of intertissue interaction between skeletal muscle and adipose tissue and are involved in the regulation of energy homeostasis, lipid metabolism, and insulin sensitivity. In obesity and type 2 diabetes mellitus (DM), the balance between these hormonal signals is disrupted, which contributes to the formation of leptin resistance, dyslipidemia, and the progression of cardiometabolic risk. At the same time, clinical data on the role of irisin as a marker of metabolic dysfunction remain controversial. Objective: to assess irisin and leptin levels in patients with type 2 DM and/or obesity and determine their relationships with lipid profile parameters. Materials and methods. The open prospective study included 99 individuals (27 men and 72 women), including 87 patients with type 2 DM and/or obesity and 12 practically healthy individuals in the control group. Serum irisin and leptin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Biochemical analysis of the lipid profile was performed: total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglycerides. Statistical analysis was performed using the SPSS 26.0 package using the t-test, one-way ANOVA with post hoc Tukey HSD test, Pearson correlation analysis, and multivariate linear regression. Results. Patients with obesity and/or type 2 DM had significantly higher leptin levels and pronounced lipid profile abnormalities compared with practically healthy individuals. The highest leptin concentrations were observed in the obese group. Bivariate analysis demonstrated a statistically significant positive relationship between irisin levels and HDL-C (r=0.63; p<0.05), which may indicate its potentially protective role in the formation of a favorable lipid profile. According to the results of multivariate regression analysis, leptin was an independent negative predictor of irisin levels. Obesity without carbohydrate metabolism disorders was associated with increased irisin levels, while the combination of obesity with type 2 DM, especially in the first-detected forms, was accompanied by a decrease in its concentration. Conclusion. Irisin levels reflect the phase nature of changes in metabolic status during the progression of obesity and type 2 DM and can be considered as an integrative marker of intertissue regulation between muscle and adipose tissue in cardiometabolic diseases.