: Current literature indicates a correlation between type 2 diabetes mellitus (T2DM), Helicobacter (H) pylori infection, and chronic inflammation. Antidiabetic therapies were involved in metabolic strategies for mitigating chronic inflammation. The current study aims to assess the impact of antidiabetic therapies on lipids and adipocytokines production in T2DM patients with H. pylori infection. The study was conducted on 127 participants allocated to 102 T2DM patients and 25 healthy subjects. The diabetic patients were subdivided into six groups according to metformin administration (mono, and dual therapy). Diabetic untreated patients showed significant (P< 0.001) elevations in the levels of body mass index, microalbuminuria, blood glucose, glycosylated hemoglobin (HbA1c), H. pylori immunoglobulin-G, and lipid profile parameters compared to healthy controls. Moreover, C-reactive protein (CRP) and leptin concentrations exhibited a significant (P< 0.001) increase, while adiponectin levels observed a marked (P< 0.001) decrease in diabetic patients compared to healthy controls. Treatment with antidiabetic therapy showed a significant (P< 0.05) amelioration in the levels of blood glucose, HbA1c%, cholesterol, low-density lipoproteins (LDL), cardio-risk factors, CRP, leptin, and adiponectin compared to diabetic-untreated patients. Notably, H. pylori infection revealed noticeable positive correlations with HbA1c%, CRP, triglycerides, and leptin/adiponectin ratio in all treated-diabetic groups. The study reveals the synergistic impact of T2DM with H. pylori infection in the increased inflammatory condition and diabetic complication. The marked amelioration in the glycemic state after treatment with antidiabetic therapies was associated with improvement in lipids, CRP, and adipocytokine levels among diabetic-treated patients with H. pylori infection..