The menopausal transition is often accompanied with distressing manifestations, such as vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 polyunsaturated fatty acids (-3 PUFAs) have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of -3 PUFAs supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic literature search of randomized controlled trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 identified studies, nine studies met the inclusion criteria and were incorporated into this systematic review. Notably, four studies detected potential benefits of -3 PUFAs in improving hot flashes and night sweats. On the contrary, sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales, such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, we found inconclusive evidence of -3 PUFA’s impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of -3 PUFAs in improving vasomotor symptoms, sleep quality, and depression. Further well-designed randomized clinical trials with larger participant groups are crucial to validate and generalize these results. Review Registration: PROSPERO registration no: CRD42023421922.