Background Desmopressin acetate was recommended for nocturia in benign prostatic hyperplasia (BPH) patients recently, but its effect and safety is still controversial. We aimed to establish a systematic review and meta-analysis to confirm its effect on symptom relief and adverse effects. Methods A systematic search was performed in PubMed, Cochrane Library, EMBASE, Medline, Web of Science and Science Direct databases from January 2000 to October 2021 for controlled trials of BPH patients comparing oral desmopressin with control groups. The mean difference (MD) and odds ratio (OR) were meta-analyzed. Results Four articles with 500 patients were included. Significantly greater benefit was detected for the desmopressin group in the improvement of nocturia (P = .004), international prostate symptom score - storage (IPSS-S) (P = .03), and quality of life (QoL) (P = .04) scores. Patients treated with desmopressin were at higher risk than the control group for short-term adverse events (P < .001), including nausea (4.71%, P = .04), headache (20%, P < .00001), dizziness (5.88%, P = .02) and hyponatremia (4.71%, P = .04), but the long-term incidence might decrease. Conclusion Desmopressin acetate can reduce nocturia frequency and improve the IPSS-S and QoL score in BPH patients. Some adverse reactions of desmopressin, such as hyponatremia, headache, dizziness and nausea, may be mild and short-term. No significant difference of desmopressin was found in improving the overall IPSS score and maximum urine flow.