Climate change and food security issues have increased the demand for effective and sustainable technologies in the food and agriculture sectors. Plasma-activated water (PAW), a novel cleaning and disinfecting agent enriched with reactive oxygen species and reactive nitrogen species, has attracted widespread attention due to its potential application in maintaining microbiological safety and other quality parameters of food products. Compared to traditional disinfection methods, PAW is rapid and effective for various products, unrestricted by the volume or shape of the treated sample, and is green and sustainable. This article reviews research progress on latest preparation methods, physicochemical properties, antimicrobial activities, potential antimicrobial mechanisms of PAW, and their applications in the food industry. In addition, current methods for preparing PAW suffer from low efficiency, poor antimicrobial stability, and a lack of technology validation and safety evaluation. To solve these challenges, the synergies between PAW and other technologies, the impact on food quality, and current methods for assessing the safety of PAW are highlighted. Technology readiness, energy consumption, international regulations, toxic intermediate products during PAW production, scalability, and important directions for future research on the commercialization of PAW are also presented. It provides the necessary theoretical basis for regulating the generation of high-throughput PAW and demonstrates the feasibility of PAW as a novel food cleaning and sanitizing agent. In summary, this review provides essential insights into PAW's safety, application potential, and sustainability for the food industry.