Background <p>Current evidence regarding the efficacy of desmopressin in combination therapy for nocturnal polyuria (NP) in elderly patients remains limited. This meta-analysis aimed to evaluate the efficacy and safety of desmopressin combined with different medications for treating NP in the elderly population.</p> Methods <p>A systematic search was conducted across CNKI, PubMed, the Cochrane Library, Scopus, Web of Science, Wanfang Data, and VIP databases for randomized controlled trials (RCTs) published up to February 2025 that evaluated desmopressin-based combination therapy in participants with a mean age ≥ 55 years and a primary diagnosis of nocturnal polyuria. This study adhered rigorously to the PRISMA guidelines. The quality of the studies included in the review was assessed. Data on therapeutic effectiveness and the incidence of adverse events were extracted and analyzed.</p> Results <p>Two studies involving a total of 133 elderly patients (72 in the combination therapy group and 61 in the monotherapy group) were included. The results indicated that desmopressin tablets combined with other drugs significantly reduced nocturnal voiding frequency (<i>P</i> = 0.002) and nocturnal urine volume (<i>P</i> &lt; 0.0001) compared to monotherapy with an α-blocker or tolterodine. No significant increase in adverse events was observed in the combination therapy group.</p> Conclusion <p>This meta-analysis provides the first comprehensive evaluation of desmopressin combination therapy for nocturnal polyuria, confirming its potential efficacy, particularly in the 60–70 age group. However, given the limited data, these findings are preliminary and require validation in larger, well-designed multicenter RCTs with standardized outcome definitions.</p>