Background: Lifestyle plays an important role in preventing and managing gastroesophageal reflux disease (GERD). In response to the conflicting results in previous studies, we performed a systematic review and meta-analysis to investigate this association. Methods: Relevant studies published until January 2023 were retrieved from 6 databases, and the prevalence of symptomatic gastroesophageal reflux (GER) or GERD was determined from the original studies. A random effects model was employed to meta-analyze the association by computing the pooled relative risk (RR) with 95% confidence intervals (95%CIs). Furthermore, subgroup and dose–response analyses were performed to explore subgroup differences and the association between cumulative physical activity (PA) time and GERD. Results: This meta-analysis included 33 studies comprising 242,850 participants. A significant negative association was observed between PA and the prevalence of symptomatic GER (RR = 0.74, 95%CI: 0.66–0.83; p < 0.01) or GERD (RR = 0.80, 95%CI: 0.76–0.84; p < 0.01), suggesting that engaging in PA might confer a protective benefit against GERD. Subgroup analyses consistently indicated the presence of this association across nearly all subgroups, particularly among the older individuals (RR