Cold plasma is an emerging non-thermal processing technology that could fulfill the food industry’s need for decontamination purposes without compromising the quality if optimized in terms of plasma parameters, including feed gases, voltage, and exposure time. Different food matrices require specialized optimized processes due to the interactions between plasma and the food. In the present study, the response surface methodology was applied to optimize the radiofrequency low-pressure cold plasma processing of saffron (Crocus sativus L. stigmas.) with the aim of achieving the highest decontamination level with the least harm to metabolites. The effects of the treatment time, power, and three gas mixtures (X, Y, and Z) consisting of air, oxygen, and argon on 22 responses related to microbial load and quality of saffron were evaluated in 42 experiments. Eleven critical responses that determine the final quality of saffron were considered to calculate the desirable function as a comprehensive approach for optimization. Analyses showed that all factors significantly affected the desirable function, and the fitted linear model was significant. The optimal condition was determined as an RF power of 76 W for 26 min using the “Y” gas mixture, which reduced the total microorganisms, coliforms, Escherichia coli, molds, and yeast by 5.75, 6.71, 6.07, and 4.00 log CFU g−1 respectively. The optimal condition preserved saffron quality within category I of the ISO specification No. 3632-1. The experimental values were in accordance with the predicted values. Optical emission spectroscopy revealed that the main plasma reactive species were Ar+ species, monoatomic oxygen, O2+, O+ ions, excited N2 species, and N2+ ions. The temperature of the samples after treatment was in the range of 40–44 °C. Scanning electron microscopy of the saffron threads indicated surface etching. Our findings showed that saffron was disinfected without substantial harm to its appearance and metabolites by applying appropriate plasma treatment.

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