This study was performed to study the in vitro and in vivo efficacy of hydroalcoholic extract of curry leaf (CLE) rich in carbazole alkaloids, against LPS‐induced inflammation in Raw 264.7 macrophages and cerulein‐induced acute pancreatitis, respectively. CLE was characterized by Fourier‐transform infrared (FTIR) and liquid chromatography–mass spectrometry. Raw 264.7 cells were stimulated with LPS (2 μg/ml) and treated with CLE. The animals were treated with two doses of CLE (100 and 300 mg/kg). Plasma biochemistry, tissue lipid peroxidation, cytokines, and histological examination were evaluated. CLE was found to decently scavenge the activity of DPPH radical. It dose dependently suppressed nitrite production and oxidative stress in macrophages. CLE alleviated LPS‐induced inflammation in macrophages as evident from the results of various inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α). In vivo, CLE reduced cerulein‐induced pancreatic edema. CLE significantly abrogated the cerulein‐induced lipid peroxidation, nitrite, MPO, and GSH levels. The inflammatory cytokines and p65‐NFκB activity were significantly reduced by CLE. Mechanistically, CLE reduced the expression of NT, MPO, IL‐1β, ICAM‐1, and COX‐2, and increased the expression of Nrf2. It reduced distant organ damage markers as well. We report for the first time that CLE holds substantial potential for the prevention of acute pancreatitis.