Background: Identification of the pathogenesis of metabolic derangement in obesity is important. MicroRNA-26a has a regulatory function in glucose and lipid metabolism. Glycogen synthase kinase 3β (GSK-3β) represents a target gene of MicroRNA-26a.Objectives: Our aim was to measure serum MicroRNA-26a and GSK-3β in women with obesity and detect their correlation to clinical and metabolic variables in this group of patients.Methods: In total, 70 obese females and 25 healthy non-obese females were involved in this cross-sectional study. Blood pressure, BMI, waist circumference, and thicknesses of triceps, subscapular, and suprailiac skinfolds were measured. The HbA1c, fasting blood glucose (FBG), lipid profile, ALT, AST were measured in serum. MicroRNA-26a and GSK-3β expression were evaluated via real-time PCR.Results: In obese women, the MicroRNA-26a expression was significantly decreased, and the GSK-3β expression level was significantly raised compared to healthy control (P < 0.001; for both). MicroRNA-26a had significant negative correlation to age (r = –0.260; P = 0.030), ALT (r = –0.300; P = 0.012), FBG (r = –0.353; P = 0.003), HbA1c (r = –0.588; P < 0.001), triglycerides (TG) (r = –0.347; P = 0.003) and GSK-3β (r = –0.627; P <0 .001). Nonetheless, GSK-3β was significantly positively correlated to age (P < 0.001) and BMI (P = 0.022), in addition to ALT (P<0.001), HbA1c (P<0.001), TG (P<0.001). Multivariate analysis reported that age (95% CI: 1.058–1.299; P = 0.002) and MicroRNA-26a (95% CI: 0.000–0.004; P ≤ 0.001) were the significant variables correlated to metabolic syndrome (MetS).Conclusion: Serum MicroRNA-26a is significantly decreased, and serum GSK-3β is significantly escalated in obese patients. MicroRNA-26a and GSK-3β are significantly interplayed with MetS in obese patients.