Oxidative stress (OS) has been implicated as a pivotal contributor to the pathogenesis and progression of mood disorders. Uric acid (UA), the predominant non-enzymatic antioxidant in systemic circulation, exhibits robust antioxidative capacity to mitigate OS-induced damage while conferring neuroprotective effects on the central nervous system. Accumulating clinical evidence demonstrates statistically significant disparities in serum uric acid (SUA) levels among patients with major depressive disorder (MDD), bipolar disorder (BD), and healthy controls. These variations are hypothesized to stem from disease-specific dysregulation of oxidative stress intensity and adenosine homeostasis within the purinergic system. Critically, SUA level shows potential as a biomarker for distinguishing BD from MDD, particularly during early disease stages, thereby offering a novel strategy to address diagnostic challenges in psychiatric practice. This review systematically summarizes recent advances in SUA research within mood disorders, which provides important thinking for the differential diagnosis of MDD and BD in clinical practice.