Schizophrenia is a severe mental disorder and antipsychotics are drugs usually used to treat this condition. Chronic hepatitis is a condition that can significantly impair hepatic functions. Most antipsychotics are metabolized by the liver, except for paliperidone, which undergoes the least amount of hepatic metabolism. This systematic review was conducted to investigate paliperidone's effectiveness and safety in patients with schizophrenia and concurrent chronic hepatitis. A detailed search using two databases, PubMed and Google Scholar, was done from June 2022 to July 2022. The PubMed search yielded 443 results and three more results were identified from Google Scholar. After a thorough screening, seven results pertinent to our study were taken into consideration for this review. All of the studies suggested that paliperidone is a safe and effective drug for the treatment of schizophrenia and since it does not undergo major hepatic metabolism and has no drug-drug interactions with antiviral drugs given in the treatment of chronic hepatitis, It can be safely used to treat schizophrenia with chronic hepatitis as a comorbid condition.