Background Xerostomia is a common clinical condition that significantly impairs oral health and quality of life. Pilocarpine, a muscarinic agonist, is frequently prescribed to stimulate salivary secretion. Methods This systematic review and meta‐analysis was conducted in accordance with PRISMA guidelines and registered in PROSPERO. Electronic searches of PubMed, Cochrane Library, Science Direct, Scopus, Embase and Google Scholar were performed for randomized controlled trials published between January 2005 and November 2025. Trials comparing pilocarpine with placebo in patients with xerostomia confirmed by sialometry were included. Risk of bias was assessed using the Cochrane Risk of Bias (ROB) 2.0 tool. Meta‐analysis was performed using StataCorp software 2025 with standardized mean differences of salivary flow rate. Results 12 randomized controlled trials involving 599 participants were included, with 7 studies contributing to the meta‐analysis. Pilocarpine showed a statistically significant improvement in salivary flow rate compared with placebo (SMD = 0.15; 95% CI: 0.06–0.25; p < 0.001; I 2 = 98%). Subgroup analysis demonstrated a significant effect for topical pilocarpine ( I 2 = 72%), while systemic pilocarpine did not show statistical significance ( I 2 = 96%). Conclusions Pilocarpine improves salivary flow rate in patients with xerostomia, particularly when residual salivary gland function is preserved, with topical formulations showing more consistent evidence of efficacy. However, given the high heterogeneity, results should be interpreted cautiously.
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