Costus arabicus L. (C. arabicus) is a plant used in Brazilian folk medicine to treat urolithiasis; however, its mechanism of action is unclear. The interaction between calcium oxalate (CaOx) crystals and the renal epithelium is important in calculogenesis, and compounds that modulate this process represent candidate therapeutic agents for stone prevention. Therefore, we assessed the inhibitory activity of C. arabicus on CaOx crystallization and the interaction of CaOx crystals with the renal epithelium. A seeded CaOx monohydrate (COM) crystallization system was used to study the effect of C. arabicus on crystal growth. Madin Darby canine kidney (MDCK) cells were used to study [(14)C] COM crystal adhesion in the presence and absence of an aqueous extract of C. arabicus. Cytotoxicity was assessed using a tetrazolium (MTS) cell proliferation assay. Aqueous extracts of C. arabicus decreased crystal growth in a concentration-dependent fashion. Precoating crystals with C. arabicus extract prevented their adhesion to MDCK cells, while pretreating cells did not show any effect. The extract was non-cytotoxic in concentrations of at least 1 mg/ml, which is likely above concentrations achievable in the urine following oral ingestion and excretion. No inhibitory activity was found in hexane, methyl chloride, n-butanol and ethyl acetate fractions of an ethanol extract of the herb. An aqueous extract of C. arabicus may disrupt calculogenesis by interacting with CaOx crystal surfaces. Activity was present in the aqueous extract; therefore, this agent may be bioavailable when administered orally. Fractionation results suggest that the active agent might be a polar polysaccharide. Further identification and characterization along these lines may be warranted.