Oxalate exposure to human renal epithelial cells triggers a vicious cycle of oxidative stress leading to cellular injury and deposition of calcium oxalate crystals on the injured cells. This results in further oxidative damage causing inflammation and loss of cell–cell adhesion factors, ultimately leading to irreparable kidney damage. However, these events can be attenuated or prevented by plants rich in antioxidants used in the traditional system of medicine for treatment of kidney stones. To delineate the mechanism by which Bergenia ligulata extract exerts its cytoprotective role in oxalate-induced injury we designed this study. Our results revealed that oxalate-injured HK2 cells cotreated with ethanolic extract of Bergenia ligulata displayed increased viability, reduced oxidative stress due to lowered production of intracellular reactive oxygen species (ROS) and decreased apoptosis. We also observed lowered markers of inflammation, along with increased expression of epithelial marker E-cadherin and decreased expression of mesenchymal markers Vimentin, F-actin, Transforming growth factor beta 1 (TGF-β1) and EMT-related proteins in renal tubular epithelial cells through immunocytochemistry, real-time PCR and western blotting. Our findings collectively suggest that by reducing oxidative stress, modulating crystal structure and preventing crystal–cell adhesion, B. ligulata inhibits the EMT pathway by downregulating the various mediators and thereby exerts its cytoprotective effect. Graphical abstract