Calcium oxalate monohydrate (COM) crystals bind avidly to the surface of proliferating and migrating renal endothelial cells, perhaps a key event in kidney stone formation. Oxalate-induced pre-oxidative stress can further promote crystal attachment cells. Natural products including gallotannins found in green teas have been studied as potentially novel treatments to prevent crystal retention and kidney stone formation. Gallotannin significantly inhibited COM crystal growth and binding to Madin-Darby Canine Kidney Cells type I (MDCK I) renal epithelial cells at non-toxic concentrations. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that gallotannin significantly attenuated oxalate-induced mRNA and protein expressions of monocyte chemoattractant protein 1 (MCP-1), osteopontin (OPN), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22(phox) and p47(phox) in human primary renal epithelial cells (HRCs). Gallotannin also reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as enhanced antioxidant enzyme superoxide dismutase (SOD) activity in oxalate treated HRCs. Taken together, our findings suggest that gallotannin can contribute to nephrolithiasis prevention via direct effects on renal epithelial cells including suppression of COM binding and MCP-1 and OPN expression, along with augmenting antioxidant activity.