The effects of geraniin (GER), an ellagitannin extracted and purified from the rind of Nephelium lappaceum L., on ameliorating transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells were investigated. The CCK-8 cell viability assay was used to detect the effects of different concentrations of GER on cell viability, and the optimal concentration was determined. HK-2 cells were divided into five groups: control, TGF-β1 induction (10 ng/mL TGF-β1), and TGF-β1 induction+GER treatment (5, 10, and 20 μg/mL GER) groups. The expression levels of key EMT-related factors, such as α-smooth muscle actin (α-SMA), E-cadherin, and vimentin were detected using western blotting and immunofluorescence staining. The changes in the intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) content between different experimental groups were determined to evaluate the effects of GER on mitochondrial function. Compared with the model group, the high-dose GER group exhibited significantly increased E-cadherin levels (increased by 128.36%) (P<0.01) and significantly decreased vimentin levels (decreased by 47.78%) (P<0.01). Further, the immunofluorescence staining results revealed that GER reduced the protein level of α-SMA and eliminated the excessive ROS produced in TGF-β1-induced HK-2 cells. Furthermore, MMP reduction was considerably improved and the ATP level was significantly increased by 24.01% (P<0.05). In conclusion, the study findings suggested that GER could inhibit TGF-β1-induced EMT in HK-2 cells by ameliorating mitochondrial dysfunction and reducing the oxidative stress levels.