Saffron is the most expensive agricultural product in the world and Iran is the largest saffron producer in the world. Saffron contamination in different stages of its production process leads to loss of credibility in export and the global market in addition to loss of quality. Therefore, it is necessary to select an appropriate method for inactivation of the microbial flora of saffron. Among the common methods that are used for inactivation of microorganisms, cold plasma has attracted much attention due to potential benefits such as its non-toxic nature, low operational costs, significant reduction in water consumption for decontamination, and possibility of its use for a variety of food products. Plasma is a state of ionized gas including ions, electrons, ultraviolet rays, and reactive species such as radicals, atoms and molecules which can ignite and inactivate microorganisms. In this research study, cold plasma was produced using two types of gas including nitrogen and air, and the effect of plasma radiation at 0, 3, 6, 9 and 12 minutes on the chemical and microbial (Escherichia coli, Enterococcus faecalis, Mold and Yeast) properties of saffron were investigated. The results of this study showed that germicidal effects of nitrogen plasma is lower than air plasma and exposure time to plasma has a significant effect on reduction of microbial load. It was also seen that inactivation of microorganisms increases with increased time of exposure to plasma exposure. Maximum microbial reduction was observed in 12 minutes. Maximum reduction in microbial load was observed at 12 minutes and 18 kilovolt voltage, which reduced the population of Escherichia coli, Enterococcus faecalis, mold and yeast by 2. 69, 2. 48, and 1. 95 log cycles, respectively, However, with increasing radiation time, the amount of crocin, picocrocin and safranal decreased (p˂ 0. 05). Reduction of crocin, safranal and picocrocin in 12 minutes was 6. 01, 4. 04, and 5. 44%, respectively.