Background: Data on the effects of omega-3 fatty acid supplementation on clinical symptoms and metabolic profiles in patients with endometrial hyperplasia (EH) are limited. This intervention was performed to assess the effects of omega-3 fatty acid supplementation on clinical symptoms and metabolic profiles in patients with endometrial hyperplasia (EH). Methods: This randomized, double-blind, placebo-controlled trial was conducted among 40 women diagnosed with simple endometrial hyperplasia (EH). EH diagnosis was performed based on specific diagnostic procedures of biopsy. Participants were randomised into two groups to intake 1,000 mg omega-3 fatty acid supplements from flaxseed oil ( n = 20) or placebo ( n = 20), twice a day for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to determine related markers. Results: Compared with the placebo, omega-3 fatty acid supplementation significantly decreased fasting plasma glucose (FPG) (-7.1 ± 9.6 vs. +2.0 ± 4.9 mg/dL, P = 0.001), serum insulin levels (-1.5 ± 4.6 vs. +1.6 ± 3.9 μIU/mL, P = 0.02) and homeostasis model of assessment-insulin resistance (HOMA-IR) (-0.4 ± 1.1 vs. +0.4 ± 1.0, P = 0.02). In addition, a significant increase in plasma total antioxidant capacity (TAC) (+102.6 ± 69.6 vs. +5.0 ± 37.1 mmol/L, P < 0.001) and total glutathione (GSH) levels (+63.6 ± 84.9 vs. -3.0 ± 69.4 μmol/L, P = 0.01) were seen following the supplementation of omega-3 fatty acid compared with the placebo. Omega-3 fatty acid supplementation had no significant effect on regression, lipid profiles, and other biomarkers of inflammation and oxidative. Conclusions: In conclusion, we found that omega-3 fatty acid administration for 12 weeks to subjects with EH significantly improved FPG, insulin, HOMA-IR, TAC and GSH levels, but did not influence regression, lipid profiles, and other biomarkers of inflammatory and oxidative stress.