Desmodium styracifolium (D. styracifolium) has been widely used in traditional Chinese medicine for the treatment of urolithiasis. This work was undertaken to investigate extracts from different polarity fractions of D. styracifolium for possible antilithic effects as well as antioxidant potential to explore the underlying phytochemically active constituents of this plant. The extracts of D. styracifolium were divided into four different polarity fractions by petroleum ether (Fr. PE), chloroform (Fr. CH), ethyl acetate (Fr. EA), and n-butyl alcohol (Fr. NB). The antilithic and antioxidant effects were evaluated and compared in vivo on an animal model of calcium oxalate (CaOx) urolithiasis, which was established by administration of 1 % ethylene glycol along with 2 % ammonium chloride in drinking water for 28 days. A total of 60 male Sprague-Dawley rats were randomly divided into six groups: normal control group, lithogenic group, and four different polarity fractions of D. styracifolium-treated groups. At the end of the study, urine, blood, and kidney tissue samples were all collected for evaluation. Among the four polarity fractions of D. styracifolium extracts, the Fr. PE and Fr. NB treatment significantly reduced the CaOx crystal deposition in kidneys, prevented the renal toxic changes like pH, Cr, and BUN. In addition, Fr. PE and Fr. NB treatment significantly decreased urinary excretion of oxalate along with a increase of citrate excretion. The increased amounts of malondialdehyde and decreased activities of superoxide dismutase, catalase, and glutathione peroxidase were detected in lithogenic group, D. styracifolium extracts treatment prevented the oxidative stress changes especially for the Fr. PE and Fr. NB extracts. In conclusion, our data suggest that the extracts from D. styracifolium possess the antiurolithic activity, possibly mediated through the inhibition of CaOx crystal aggregation as well as the alleviation of oxidative injury in the kidney, and the Fr. PE and Fr. NB extracts are the active fractions of D. styracifolium extract.