Proton pump inhibitors (PPIs) are drugs that successfully inhibit stomach acid secretion. It is used for the management of various acid-related conditions, including gastroesophageal reflux disease (GERD) and other gastric illnesses. It can reduce hydrochloric acid output via irreversible binding to the hydrogen potassium adenosine triphosphatase (H+/K+ ATPase) and inhibiting its action in the stomach. PPIs are among the most often prescribed drugs, however, 25% to 70% of these prescriptions have no legitimate indication. As a result, patients frequently take these treatments without benefit exposing themselves to unwanted adverse events. PPIs can cause acute interstitial nephritis (AIN), which can be a serious side effect associated with acute kidney injury (AKI). It has been reported that using PPIs for a long time has been associated with an elevated risk of chronic kidney disease (CKD). As a result, this review aims to investigate the adverse effects of long-term use of PPIs on renal function