Nephrolithiasis has severe ramifications with respect to health and management cost. Current modalities of treatment though very effective in getting provisional relief from stones are not devoid of side effects and also fail to avert the recurrence, which is in fact the main concern of patients with kidney stones. Hajrul yahood, Phyllanthus niruri and Cystone have been used in folk medicine since ages and are well known for their lithotriptic and anti- urolithic properties. The present study was carried out at the animal house of Sindh Agriculture University Tando Jam to evaluate the litholytic and anti -urolithic effects of Hajrul yahood, Sang sarmahi, Phyllanthus niruri and cystone on glyoxylate induced nephrolithiatic rats. For this purpose, seventy eight male wistar rats were equally divided into thirteen groups of six rats each. Hajrul yahood, Sang sarmahi and Phyllanthus niruri were administered either alone or in combination of equal quantity of each by weight. Cystone given alone was also utilized as a standard drug to compare the effects of Hajrul Yahood, Sang Sarmahi and Phyllanthus Niruri on calcium oxalate kidney stones. Calcium oxalate crystallization was induced by intraperitoneal injections of Glyoxalate prior to start of the treatment in the litholytic groups and was administered along with the test drugs in the groups. At the completion of treatment period, serum samples from 42 rats in groups; and both the kidneys from all the experimental rats were recovered. Serum was analyzed for the activity of anti-oxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT); and levels of calcium, magnesium, oxalate and creatinine. Right kidney was homogenized with phosphate buffer saline (PBS), and centrifuged. Supernatant thus obtained was analyzed for the levels of SOD, GPX, CAT, reduced glutathione (GSH) and malondialdehyde (MDA). The left kidney was fixed in Bouin liquid, embedded in paraffin, sectioned and stained with hematoxylin and eosin H&E for histological examination under polarized light microscope. Serum analysis results showed that the activity of antioxidant enzymes and magnesiumlevel in rat groups treated with cystone, combination, HY and PN were lower in the order given as against the negative controls, but were significantly higher than that of the positive controls (p<0.05). Serum calcium level was found to be in normal range in cystone, combination, HY and PN treated groups of rats, but it was lower than normal in positive controls. Both serum oxalate and creatinine levels were detected to be significantly lower in cystone, combination, HY and PN treated groups of rats as compared with positive controls. A similar comparison of the parameters measured in tissue samples revealed that antioxidant enzyme activities and reduced glutathione level were significantly enhanced in cystone, combination, HY, and PN treated groups of rats as against the positive controls. In contrast, tissue MDA levels were seen to be significantly lower in cystone, combination, HY and PN treated groups of rats than the positive controls. Histological findings of renal tissue sections were also consistent with the serum and tissue chemistries showing lesser damage to the kidney tissue and calcification in cystone, combination and HY treated groups of rats as against the positive controls. Cystone in comparison to combined treatment exhibited better nephro-protection against hyperoxaluria induced oxidative stress because of its increased antioxidant enzyme activities and increased glutathione and magnesium levels. In conclusion, present study has demonstrated the litholytic,and nephroprotective effects of cystone, HY and PN due to their high antioxidant capacity to inhibit lipid peroxidation in glyoxylate induced hyperoxaluric rats and also due to their ability to reduce oxalate synthesis. Sang sarmahi however, in contrast to the general notion has failed to exhibit any significant litholytic and anti urolithic effects at the dose used in present study.