Sulphur dioxide (SO2) is commonly used in the wine industry to prevent oxidation and maintain microbial stability. However, it can harm consumer health, resulting in a growing demand for chemical-free wine. Therefore, reducing or eliminating the addition of SO2 has become a prevalent trend in the wine industry. In recent years, researchers have made significant progress in finding alternative methods to SO2. This review provides the latest research progress on innovative methods proposed to replace SO2 in winemaking. These include dimethyl dicarbonate, silver nanoparticles, lysozyme, chitosan, phenolic compounds, membrane filtration, ultrasound, ultraviolet irradiation, high pressure, and pulsed electric field. However, these individual antimicrobial methods do not possess the same comprehensive antimicrobial and antioxidant properties as SO2. In the proposed strategy, a promising alternative to SO2 could be to combine physical sterilization technologies with antimicrobial substances. In particular, gentle physical techniques such as pulsed electric field in synergy with natural grape polyphenols can maintain the microbiological stability of wine without the introduction of foreign aid substances, while enhancing the wine's antioxidant properties. In conclusion, while replacing SO2 entirely for wine production remains challenging, the combination of physical sterilization technologies and natural antimicrobial substances shows promise as a viable alternative.