[Background] For calcium oxalate stone, a common clinical disease with high recurrence rate, surgery is the only solution due to the hardness of the stones, from which, however, patients suffer a lot. It has been verified that intestinal flora affects the formation of calcium oxalate stones and thus reduces the incidence. [Objective] To investigate the effect of Lactobacillus plantarum (BNCC 194165) on calcium oxalate stones in mice. [Methods] For in vitro experiment, a total of 0.02 mol/L sodium oxalate was added to the MRS broth to prepare the screening medium (MRS-OX) and then 200 μL 3.48×10¹² CFU/L L. plantarum suspension was inoculated into the MRS-OX to yield the bacteria-containing medium (B+MRS-OX). MRS-OX and B+MRS-OX at equivalent volume were cultured at 37 °C for 2 days and the concentration of residual oxalic acid was measured by the oxalic acid kit. As for the in vivo experiment, 10-week-old male Kunming mice were randomized into the control (C) group, L. plantarum group (B), glyoxylic acid (GA) group, and L. plantarum+glyoxylic acid (B+GA) group, with 5 in each group. Glyoxylic acid was used to induce calcium oxalate stone in mice. A total of 200 μL 3.48×10¹² CFU/L L. plantarum suspension was given to the model mice and then the effect on calcium oxalate stones was observed. After the experiment, the variation of body weight in each group was plotted and kidney index was calculated. Then we detected the haematological indexes (creatinine, blood urea nitrogen, blood concentration of oxalic acid) and oxidative stress indexes of total superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, the pathological sections of kidney were observed and renal crystallization score was calculated. Through the above experiments, the effect of L. plantarum on calcium oxalate stone formation in mice was preliminarily explored. [Results] In the in vitro experiment, the oxalic acid-decomposing efficiency of L. plantarum in MRS-OX was 10%. In the in vivo experiment, L. plantarum significantly inhibited the weight loss of mice and reduced the levels of plasma creatinine, urea nitrogen, and oxalic acid. Pathological observation showed that the renal crystals of B+GA group were significantly reduced and the crystallization score was different from that of the GA group (P<0.01). Moreover, the oxidative stress damage of kidney caused by calcium oxalate stones was alleviated in the B+GA group. [Conclusion] L. plantarum can relieve the damage of calcium oxalate stones to kidney and reduce the generation of kidney crystals, which can be used for preventing the formation of calcium oxalate stones.