A total of 71,364 breast reductions were performed in 2022, which demonstrates a 54% increase from 2019. Women most often seek breast reduction surgery for pain, but psychological symptoms may be equally distressing, particularly those who are younger. These women may also suffer low self-esteem, inhibitions in intimacy, and reluctance to exercise, which may contribute to depressive symptoms. A systematic review was conducted using PRISMA guidelines and registered on PROSPERO (CRD42023456884). Cochrane Library, Embase, and Pubmed were searched for RCTs in English irrespective of timeframe. The studies were screened using the RoB2 tool, and data was extracted using standardized tables. The search strategy yielded 84 references, and only three were eligible for inclusion. The sample size collectively amounted to 193. The tools used to assess depressive symptoms were the Beck Depression Inventory, a modification of this tool, and the Hospital Anxiety Depression Score. All three studies showed a significant reduction in depression scores. Breast hypertrophy may cause impairment in several key psychological domains including depression, which may be relieved with surgery. Standardized assessment tools and scoring systems may enable more comprehensive evaluation and potentially lead to guidelines defining broader criteria as indications for surgery. Further investigation into the differences between women who seek breast reduction surgery versus those who do not may provide insights into other contributing factors that may be at play. Further trials should be designed with longer durations of follow-up to investigate the long-term effects of breast reduction surgery.