Background: Previous studies have demonstrated that minor salivary gland transplantation (MSGT) is an effective treatment for severe dry eye disease (DED). However, almost all studies on this procedure have been non-randomized controlled trials with small sample sizes, different first-line treatments, and uncontrolled statistical analysis, which may result in a lack of effective metrics to evaluate the efficacy and safety of LSGT. The aim of this meta-analysis was to evaluate the efficacy and safety of MSGT in patients with severe DED. Methods: PubMed, Embase, the Cochrane Library, and the Web of Science databases were systematically searched for relevant studies. Outcomes, including symptomatic improvement, changes in Schirmer test (ST) value, tear break-up time (TBUT), corneal staining (CS) value, and adverse events (AEs), were extracted for further analysis. Proportional analysis was used for binary data, and mean difference was used for continuous data. All meta-analyses were conducted using a random-effect model, and 95% confidence intervals (CIs) were included. Results: Eight studies involving 150 patients (158 eyes) were enrolled in this meta-analysis. The symptoms of DED improved in 73.6% of patients. Regarding signs, the pooled ST values improved by an average of 3.684 mm, TBUT increased by 1.823 seconds, and CS decreased by 1.966. The most common treatment-related AEs to MSGT were hypaesthesia of lip (10%), cosmetic problems (3%), and epiphora (2%). Conclusions: In summary, this meta-analysis demonstrated that MSGT can potentially treat severe DED without severe AEs.