Background Uric acid, a formerly-known antioxidant that has recently been linked with many inflammatory diseases as a pro-inflammatory and -oxidative mediator in pathological conditions. It is imperative to reassess the association between periodontitis and uric acid in locally and systematically. The aim of this systematic review was to systemically evaluate the association of periodontitis with the uric acid (UA) levels in blood, saliva and gingival crevicular fluid (GCF). Methods Relevant clinical studies up to July 1, 2022 were identified and retrieved from electronic databases, with periodontitis, uric acid, hyperuricemia and gout as the keywords. Weighted (WMD) or standardized mean difference (SMD) was calculated using fixed- or random-effect models. Methodological heterogeneity was assessed. Results Fifteen eligible retrospective studies (blood, n = 7; saliva, n = 8; GCF, n = 1) were enrolled, which included 1302 patients with periodontitis and 916 controls. Meta-analysis demonstrated a statistically enhanced blood UA content (WMD = 0.49 mg/dL, 95% CI: 0.02 to 0.96, P = 0.042) but decreased salivary UA level (SMD = -0.95, 95% CI: -1.23 to -0.68, P < 0.001) in periodontitis versus control. Statistical heterogeneity was significant among studies involving blood (I2 = 94.3%, P < 0.001) but not saliva (I2 = 33.8%, P = 0.196). Conclusions Periodontitis is associated with higher UA levels in blood and lower UA levels in saliva. The indicative mechanisms need to be verified by further clinical and experimental studies. (Registration no. CRD42020172535 in Prospero).