N-Acetylcysteine (NAC) has been investigated as an adjunctive treatment for bipolar mood disorder, particularly for its potential to alleviate depressive symptoms. The rationale stems from NAC’s role as a precursor to glutathione, a major antioxidant in the brain, and its influence on glutamatergic neurotransmission, inflammation, and oxidative stress—all of which are thought to be involved in the pathophysiology of bipolar disorder. Several randomized controlled trials have been conducted: one notable 2008 study in Biological Psychiatry found that adjunctive NAC (2g/day) significantly improved depressive symptoms over 24 weeks compared to placebo. More recent studies, however, have yielded mixed results, with some failing to replicate these benefits, especially in shorter or smaller trials. Meta-analyses and systematic reviews generally suggest that while NAC is safe and well-tolerated, the overall effect size for mood improvement is modest, and the evidence is not robust enough for unequivocal clinical recommendation. There is no significant traditional or historical use of NAC for mood disorders; its use is a product of contemporary neuroscience research. Thus, NAC is considered a promising, though not definitively proven, adjunctive therapy for bipolar depression, with further large-scale studies needed to clarify its efficacy.