BACKGROUND: Pramipexole is thought to exert antidepressant effects in patients with Parkinson's disease (PD) and depression, but its efficacy compared with typical antidepressants is unclear. This meta-analysis aims to directly compare the safety and efficacy of pramipexole and antidepressants for depression in PD patients. METHODS: Twelve electronic databases including Cochrane, PubMed, Embase, Web of Science, CINAHL, PsycINFO, ProQuest, Open Grey, CBM, The CNKI, Wan Fang Data and VIP, and two clinical trial registry websites were systematically searched up to December 30, 2024. The primary outcomes were severity of depression (change in depression rating scale) and tolerability (discontinuation for any reason at the end of treatment). Secondary outcomes included changes in motor symptoms and adverse effects. This study was registered in PROSPERO (reference number: CRD42024525826). RESULTS: A total of 12 randomized controlled trials involving 772 participants were included. There was no significant difference in the efficacy between pramipexole and antidepressants in the treatment of PD patients with depression (SMD -0.14,95 % CI -0.48 ∼ -0.21, P = 0.45) and they did not differ significantly in terms of tolerability (OR 0.78, 95 % CI 0.36-1.71, P = 0.54, I2 = 26 %). Pramipexole significantly improved motor symptoms better (SMD -0.44, 95 % CI -0.82 ∼ -0.05, P = 0.03) and decreased the incidence of anorexia (P = 0.05), but had a similar risk of other adverse effects as antidepressants. CONCLUSION: Pramipexole has an antidepressant effect similar to typical antidepressants while improving motor symptoms in PD patients. Both of them are well tolerated, and may be associated with some common adverse effects, such as anorexia, nausea, and vomiting.