Background <p>Current data indicate that supplements such as folic acid play a significant role in treating chronic atrophic gastritis (CAG). However, no meta-analysis article evaluates its efficacy comprehensively. Therefore, we conducted a meta-analysis to compare the effectiveness and safety of folic acid in the treatment of CAG with Helicobacter pylori (H. pylori) infection.</p> Methods <p>Using a systematic review method, consider randomized controlled trials (RCT), including clinical trial reports, unpublished clinical trial data, and conference papers. A comprehensive search of the literature was conducted from all years up to June 2024. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Vip, and Wanfang databases. Data were extracted using a pre-designed extraction tool and analysis was undertaken using RevMan5.4 and STAT15.1. Efficacy and safety outcomes were evaluated using risk ratio (RR) and 95% confidence intervals (CI).</p> Results <p>16 randomized controlled trials with 1364 patients were included. Compared with conventional therapy, folic acid therapy had a higher total effective rate (95.09% vs.79.06%, pooled RR = 1.19, 95% CI: 1.12–1.26, <i>p</i> &lt; 0.00001) and lower incidence of adverse events (11.64% vs. 14.04%, RR = 0.86, 95% CI: 0.46–1.60, <i>p</i> = 0.64). Moreover, folic acid can better improve gastric function and repair gastric mucosa (MD = 27.20, 95%CI:23.84–30.56, <i>p</i> &lt; 0.00001).</p> Conclusions <p>For HP-related CAG, anti-HP treatment and folic acid supplementation should be started as early as possible. Gastric mucosal protective agents can improve the curative effect and can be selected according to the condition of patients with obvious adverse reactions. Our study provided evidence for their potential clinical use in the management of CAG. However, CAG-related studies in other countries and regions need to be further studied.</p> Registration <p>The logn number of our Meta-analysis on PROSPERO is 42,024,571,785.</p>