This study aimed to investigate Ganoderic acid A’s (GAA) possible effects on inflammation and oxidative stress of caerulein-stimulated pancreatic acinar cells and uncover its effects on acute pancreatitis (AP). A cell model of AP was constructed by treating pancreatic acinar AR42J cells with caerulein. Cell counting kit-8 (CCK-8) assay was used to measure cell viability, while Enzyme-Linked Immunosorbent Assay (ELISA) and 2′,7′-Dichlorofluorescein (DCF) fluorescence assays were used to measure inflammation and oxidative stress. Western blot analysis was used to investigate Nuclear Factor-kappa B (NF-κB) signaling pathway inhibition, focusing on p65 and NF-kappa-B inhibitor alpha (IκBα) phosphorylation states. GAA significantly enhanced cell viability in caerulein-stimulated pancreatic acinar AR42J cells. It also significantly reduced AR42J cells’ inflammatory response. Furthermore, GAA treatment mitigated oxidative stress by decreasing Reactive oxygen species (ROS) production. Lastly, GAA inhibited the NF-κB pathway, as evidenced by decreased p65 and IκBα phosphorylation. By inhibiting NF-B-mediated inflammation, GAA attenuated caerulein-induced AP.