Background: Chronic kidney disease is common in cats and dogs. The diagnosis previously relied upon serum creatinine; however, symmetric dimethylarginine (SDMA) may identify chronic kidney disease (CKD) earlier. A recent evidence summary questioned the superiority of SDMA in cats. Another study raised concerns over the specificity of SDMA in dogs. Methods: Electronic databases and grey literature were systematically searched for all relevant studies up to October 2024. Studies were included based on prespecified criteria by two independent reviewers. Studies were assessed for risk of bias and applicability concerns. Results: Eleven studies were included: five in cats (481 animals) and six in dogs (460 animals). There was marked heterogeneity in the design, population and tests used. Nine studies were at high risk of bias, and nine had high applicability concerns. There was marked variation in sensitivity and specificity. Heterogeneity and risk of bias present precluded meta-analysis. Sources of heterogeneity were explored. Limitations: Grey literature searching, data extraction and risk of bias assessment lacked independent duplication. Conclusion: Significant uncertainty remains regarding the diagnostic accuracy of SDMA in CKD in cats and dogs. Well-designed diagnostic accuracy trials in clinically relevant populations with optimised reference standards and thresholds are needed. The use of SDMA may increase the risk of misdiagnosis and overdiagnosis of CKD.