Background: Antimicrobial therapy against oral pathogens is a common way to prevent or treat mouth diseases. Because of increasing resistance to synthetic medicine, herbal drugs are being used more and more. Material and Methods: Hydroalcoholic extract of powdered stigma from saffron flower was provided and used to prepare fractions in petroleum-ether, chloroform, and ethanol solvents respectively. Growth inhibition zone, MIC and MBC of the mentioned fractions were determined against Strep. mutans, Strep. sanguinis, Strep. salivarius, Strep. sobrinus, and E. faecalis and compared to those of chlorhexidine and ampicillin. Results: The hydroalcoholic extract, and ethanolic and chloroformic fractions of crocus sativus linn had antimicrobial effects, despite its petroleum etheric fraction and distillate. The best effect of hydroalcoholic extract was on Strep. sanguinis with the MIC and MBC of 31.25 mg/ml both. Maximum inhibitory effect of ethanol fraction was on Strep. sanguinis with MIC and MBC of 7.81 and 15.62 mg/ml respectively. Chloroform fraction presented most effect on Strep. sanguinis presenting MIC and MBC of 7.8 mg/ml. Conclusion: Crocus sativus linn contains agents with antimicrobial properties against some oral pathogens, particularly streptococcus sanguinis. It may be used to prepare antimicrobial drugs and mouthwashes in the future.