Ready-to-eat wine-pickled mud snails (Bullacta exarata) typically host a large number of microorganisms and are frequently contaminated with pathogenic bacteria during processing, resulting in a higher risk for foodborne illness with consumption. In this study, the decontamination effects of different treatment methods, including the use of ultrasonic cleaning (USC), natural chemicals, and ultra-high pressure (UHP), on the quality and safety of pickled mud snails were investigated by assessing the total viable count (TVC), total volatile base nitrogen (TVB-N) content, thiobarbituric acid-reactive substance (TBARS), and pH value of the products after 12 months of storage at −20 °C. Treatment with 200 W USC for 5 min was the most effective approach for reducing TVC in raw mud snails, with a minimal change in food quality. Natural chemical treatment or UHP treatment significantly inhibited the increase in TVC, pH, and TBARS and TVB-N accumulation compared with the control group; however, their combined treatment had no synergistic effect. In contrast, the combined chemical treatment was more effective in inhibiting changes in the above indices in pickled mud snails than UHP treatment alone or combined chemicals + UHP treatment. In addition, the bacterial diversity of pickled mud snails before and after 12 months of storage at −20 °C was determined using Illumina MiSeq sequencing. Our results indicated that USC combined with natural chemicals can be utilized commercially to maintain the quality and safety of pickled mud snail during storage at −20 °C.