The purpose of this study was to investigate the anti-inflammatory effect of an aqueous extract of seed of broccoli (AESB) in Helicobacter pylori (HP)-infected patients without atrophic gastritis. This was a double-centre, randomized, double-blind, controlled study. A total of 110 HP-infected subjects were randomized to receive either AESB or placebo for 2 months. Inflammatory cytokine (IL-8, IFN-γ, TNF-α, CRP, IL-17A, IL-1β, IL-18), pepsinogen I, II (PG I, PG II), and gastrin-17 (G-17) measurements and 13C-urea breath tests were performed at baseline and at 60 days. At 60 days, there was no significant difference in any of the inflammatory cytokines, pepsinogen or gastrin between the two groups. However, IL-8, IFN-γ, PG I, PG I/PG II ratio (PGR), and G-17 were reduced by 9.02 pg/mL, 5.08 pg/mL, 24.56 ng/mL, 1.75 and 0.3 pmol/L, respectively, in the AESB group compared with baseline (all P < 0.05). The HP eradication rates in the AESB group and placebo group were 11.11 and 3.70% at 60 days, respectively (P > 0.05). No treatment-related adverse events were reported. Thus, AESB may reduce the risk of gastric mucosal lesions and decrease the risk of gastric cancer by relieving inflammatory cytokines. The safety profile of AESB was satisfactory. This study is registered with the Chinese Clinical Trials Registry (Registration No. ChiCTR2100054249).© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.