Purpose: To assess the effects of Serenoa repens alone or in combination with other phytotherapy compared to placebo in men with LUTS due to benign prostatic enlargement. Materials and Methods: Following a registered protocol (CRD42021226655), we searched (December 2020) MEDLINE, CENTRAL, Embase, ClinicalTrials.gov, WHO-ICTRP trials platform and other sources with no restrictions on language, publication date or status. We included randomized controlled trials, and we critically appraised them using the Cochrane Tool for Risk of Bias Assessment (RoB 2). We conducted random-effects meta-analysis when appropriate. The primary outcomes included urinary symptoms score, quality of life, and adverse events. The certainty of the evidence was rated using GRADE. Results: We included 27 trials with 4,853 participants. S. repens results in little to no difference in urinary symptoms, quality of life, and adverse events at short- and long-term follow-up. S. repens combined with other phytotherapy may slightly reduce urinary symptoms at short-term follow-up, but the results are uncertain. The results on quality of life and adverse events are also very uncertain. Conclusions: S. repens alone may result in no clinical benefits for men with LUTS. There is greater uncertainty in the effects of S. repens in combination with other phytotherapy.