Saffron, similar to numerous other agricultural commodities, is susceptible to microbial contamination during cultivation and postharvest handling. Cold plasma treatment has emerged as an effective method for microbial inactivation while preserving food quality. The aim of this research was to preserve the color integrity and minimize the presence of microorganisms in dried saffron stigma by implementing cold plasma pre‐treatment. Process parameters were optimized using the response surface method (RSM), considering the type of atmosphere (argon and air), plasma exposure time (1, 5, and 10 min), and plasma power (40, 70, and 100 W) as independent variables. The objectives were to maximize crocin content and minimize the total microbial load. The analysis of the response surface revealed that the argon atmosphere had a more significant impact on reducing microbial contamination than air, and an increase in plasma exposure time led to a decrease in microbial load. The maximum reduction in microbial load, by 0.9 logarithmic cycles compared to the control, was achieved with a 10‐min treatment at 40 W power. Extended plasma exposure durations led to a minor reduction in the color, taste, aroma, and antioxidant properties of saffron stigma. Specifically, the color, taste, and aroma decreased by 0.5%, 0.5%, and 0.08%, respectively, with longer plasma exposure times. The antioxidant activity decreased by 0.64% with prolonged exposure time. However, the plasma‐treated samples did not show any signs of Escherichia coli, mold, or yeast. Furthermore, our findings demonstrated that the type of atmosphere significantly influenced the reduction of infection and maintenance of saffron stigma's color quality. Cold plasma pretreatment holds promise as a viable method for preserving the physicochemical attributes of saffron while effectively reducing microbial contamination.