The study was carried out to determine the in vitro effect of Plantago major extract on calcium oxalate crystals and to compare the effects of Plantago major extract with clinically used drugs like allopurinol and potassium citrate (positive controls). Modified Schneider slide gel method was used for the in vitro study and the crystals formed were measured by Image Analyser system KS 300, 3.0 Carl Zeiss. The concentrations of Plantago major extract used were from 100ppm to 350ppm. Plantago major extract at concentrations in the range of (100ppm-350ppm) significantly inhibited the size of calcium oxate crystals (dihydrate variety) against negative control (p<0.05) and against positive controls (p<0.05). However the inhibition concentration 50 (IC(50)) values on the size of calcium oxalate crystal for the extract, potassium citrate and allopurinol were 300ppm, 350ppm and 450ppm respectively. Extract of Plantago major also has inhibition effect on the number of crystals but it was not significant. In conclusion extract of Plantago major was better than allopurinol and potassium citrate in inhibiting the size of the calcium oxalate crystal in-vitro.