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Background: Helicobacter pylori (H. pylori) plays the primary role in increasing oxidative stress and causing stomach inflammation, peptic ulcers, and gastric malignancy in the infected patients. L-arginine (Arg) has antibacterial and anti-inflammatory effects. Objectives: The current study aimed at investigating the beneficial effects of L-arginine on inflammation and oxidative stress in patients infected with H. pylori with dyspeptic symptoms. Methods: The current randomized, double-blind controlled, clinical trial was conducted on 34 patients with H. pylori infection referred to the center of digestive disorders affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, in order to undergo endoscopy from December 2016 to September 2017. Patients were classified into two groups (control and treatment); the control group only received triple-drug therapy (including Amoxicillin, Clarithromycin, and Omeprazole), and the treatment group received standard triple-drug therapy and L-Arg capsules for three weeks. Gastric biopsies and serum samples were taken from all patients before and after the study. H. pylori infection was examined by a rapid urease test and antioxidant indices including superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC) were evaluated in gastric biopsies. In addition, serum samples were used to measure the inflammation factors including interleukin (IL)-8 and tumor necrosis factor (TNF)-α. Results: Level of SOD activity increased significantly in the treatment group compared with that of the control group (4.91 ± 95.21 vs. 4.0 ± 44.11 IU/mg) (P = 0.001). In the treatment group, compared with the control group, the level of TAC increased significantly (0.35 ± 0.60 vs. 0.30 ± 0.9 mM/L) (P = 0.006) and the level of GPX activity increased significantly in the treatment group compared with the control group (10.68 ± 2.39 vs. 5.16 ± 2.12 IU/mg) (P = 0.000). Regarding the inflammation factor, IL-8 decreased significantly in the treatment group compared with the control group (8.00 ± 1.94 vs. 10.28 ± 2.10 pg/mL) (P = 0.002); also TNF-α decreased significantly in the treatment group compared with the control group (9.71 ± 2.69 vs. 12.24 ± 3.29 pg/mL) (P = 0.036), while there was no significant difference in high sensitivity C-reactive protein (hs-CRP) decrease between the treatment and the control groups (2.34 ± 1.28 vs. 3.04 ± 1.58 mg/L) (P = 0.16). Conclusions: Consumption of L-arginine increased antioxidant indices and decreased inflammation in patients infected with H. pylori.