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BackgroundIt is difficult to conduct the precise diagnosis of post-stroke depression (PSD) in clinical practice due to the complex psychopathology of depressive disorder. Several studies showed that gas chromatography–mass spectrometry (GC-MS)-identified urinary metabolite biomarkers could significantly discriminate PSD from stroke survivors.MethodsA systematic review was performed for the keywords of “urinary metabolite” and “PSD” using Medline, Cochrane Library, Embase, Web of Science, PsycINFO, Wanfang, CNKI, CBM, and VIP database from inception to 31 March 2022.ResultsFour related studies were included in the review. Differential urinary metabolites including lactic acid, palmitic acid, azelaic acid, and tyrosine were identified in all the included studies. As a significant deviation in the metabolite biomarker panel, glyceric acid, azelaic acid, phenylalanine, palmitic acid, pseudouridine, and tyrosine were found in at least 2 included studies, which indicated good potential for the differentiation of PSD.ConclusionThe systematic review provided evidence that differential urinary metabolites analyzed by the GC-MS-based approach might be used as a biomarker for the diagnosis and prognosis of PSD.