Objective: This study aimed to investigate the impact of a 12-week moderate-intensity exercise intervention on the serum Irisin, osteocalcin (OC), and adiponectin (ADP) levels and their relationships with glycolipid metabolism, islet beta-cell function, and insulin resistance status in patients with type 2 diabetes (T2DM). Methods: 60 patients with T2DM were randomly assigned to an exercise group (EG, n=30) and a control group (CG, n=30). 20 age-matched healthy individuals were recruited for a normal control group (NCG). The T2DM EG underwent a regular exercise intervention for 12 weeks. Their pre- and post-training anthropometric and biochemical indicators and their serum irisin, OC, and ADP levels were determined. Results: the baseline irisin and ADP levels in the T2DM groups were lower than they were in the NCG (P<0.05). The post-training irisin and ADP levels in the T2DM EG were significantly increased (P<0.05), and there were no changes in the OC levels (P>0.05). The BMI, HbA1C, FPG, 2 h PBG, HOMA2-%B, and HOMA2-IR levels were significantly improved compared with their pre-training levels and with the T2DM CG's levels (P<0.05). A correlation analysis showed that the serum OC levels were negatively correlated with the FPG, 2 h PBG, and HOMA2-IR levels in the T2DM patients and positively correlated with the serum ADP and irisin levels (P<0.05). The serum irisin level was negatively correlated with the 2 h PBG level and positively correlated with the serum ADP level (P<0.05). The OC change rate was positively correlated with the FCP and HOMA2-IR change rates (P<0.05). The irisin change rate was negatively correlated with the FPG and HOMA2-IR change rates and positively correlated with the ADP change rate (P<0.05). Conclusion: Regular exercise results in an improvement of the serum irisin and ADP levels, the systemic metabolic markers, the islet beta-cell function, and insulin resistance in patients with T2DM.