Background despite its central role in drug metabolism the exact prevalence estimates and factors impacting on the global trends of polypharmacy in patients with chronic liver disease has remained unexamined. Methods We carried a comprehensive search of relevant databases (PubMed; EMBASE, Science citation index Cochrane Database of Systematic Reviews; and database of abstracts of reviews of effectiveness for studies since inception to and 30th May 2022 that reported on patients with chronic liver disease for which data on the prevalence estimates of polypharmacy (ingestion of > 5 non-ART was available. We subsequently carried out a systematic review and weighted meta-analysis to ascertain the exact prevalence of polypharmacy amongst patients with chronic liver disease. We evaluated the heterogeneity between studies with \({I}^{2}\) and \({\tau }^{2}\) statistics. Results Fifty studies were identified from initial literature, out of which 7 (enrolling N = 521435 patients with Chronic Liver Disease met the inclusion criteria; of this 58.7% were males, with mean age of 53.9 (± 12.2) years. The overall pooled prevalence of polypharmacy amongst patients with chronic liver disease was 31% (95% CI: 4% − 66%) (I2 = 100%, τ2 = < 0.001, p = < 0.0001). we found a higher pooled prevalence estimates amongst patients aged 50 years and older compared to their younger cohorts (42%, [CI 10–77]; I2 = 100%, P = < 0.001 vs. 21%, [CI 0–70]; I2 = 100%, P = < 0.001). Conclusion In an examination of multiple community and hospital-based databases of patients with chronic liver disease, we found a pooled prevalence estimate of polypharmacy at about 31%. This represents a case burden within the range reported in the general population and will respond to mitigation strategies thus far employed for patients in that population.