Coronavirus disease 2019 (COVID-19) developed into a pandemic within months. SARS-CoV-2 testing measures and vaccines became quickly accessible. However, due to pre- or asymptomatic transmission, effective disease control remains challenging. To complement conventional testing methods, scientists around the world have investigated dogs’ olfactory capability for true real-time detection. Several diseases are known to produce specific scents in affected individuals, excreted as volatile organic compounds, which can be easily detected by dogs within seconds. This systematic review evaluates the current evidence for using dogs’ olfactory system as a reliable COVID-19-screening tool. Two independent procedures for study quality assessment were used: the QUADAS-2 tool for the evaluation of laboratory tests’ diagnostic accuracy, designed for systematic reviews, and a second system for the general evaluation of canine scent detection studies, adapted with a focus on medical scent detection. Twenty-seven studies from thirteen countries were evaluated. Particular attention was paid to potential confounding factors, e.g., study design, patient/sample selection, dog characteristics, training protocols, and sample types/treatment. These analysis systems revealed that respectively four and six studies had low risk of bias and high quality. The four QUADAS-2 non-biased studies resulted in sensitivity and specificity ranges of 81–97% and 91–100%, whereas the six high quality studies according to the general evaluation system revealed sensitivity and specificity ranges of 82–97% and 83–100%, respectively. The other studies contained high risk of bias, concerns about the methodological applicability and/or quality concerns. Standardization and certification procedures as used for canine explosives detection should be established for medical scent detection dogs in order to use their undoubtful potential in an optimal and structured way. ‘