Pancreatin is a natural mixture of digestive enzymes derived from the pancreas of vertebrates. Recent studies have demonstrated that pancreatin has protective effects against various types of hepatic ischemia-reperfusion (I/R) injury. In this review, we summarize the existing evidence regarding the protective effects of pancreatin on hepatic I/R injury. We discuss the potential mechanisms behind the protective effects of pancreatin, including its anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrotic effects. Moreover, we discuss the potential application of pancreatin as a therapeutic agent in the treatment of I/R injury in the liver. Numerous studies have shown that pancreatin can protect against hepatic ischemia-reperfusion (I/R) injury by targeting multiple pathways and processes involved in I/R injury, including reduction in oxidative stress, suppressing inflammatory response, promoting cell proliferation as well as improvement in apoptosis process. In addition, pancreatin has a protective effect on liver injury by promoting the antioxidant defence system, inhibiting the accumulation of intracellular lipid peroxides, and restoring cellular antioxidant status. Thus, pancreatin may be a promising and effective treatment for hepatic I/R injury, and further research is needed to explore its clinical efficacy. In conclusion, pancreatin is a potential natural remedy that has been studied to potentially reduce hepatic I/R injury. Although further research is needed to confirm the efficacy of pancreatin in clinical settings, it has been suggested that it can act as a natural remedy for hepatic I/R injury due to its multiple mechanisms of action and its ability to restore the balance of oxidative stress. Pancreatin has been studied as a potential natural remedy for hepatic I/R injury due to its ability to inhibit lipid peroxidation, promote antioxidant defence system activity, and restore cellular antioxidant status. Keywords: Pancreatin, hepatic ischemia-reperfusion, antioxidant activity, PI3K-AKT pathway, hepatoprotective strategies.