Red dragon fruit juice (RDFJ) is a common fruit processing product on the market, and different processing methods can affect its quality. This study selected traditional thermal processing methods such as pasteurization and novel non-thermal processing methods like ultrasonication and cold plasma to treat red dragon fruit juice. The effects of different processing methods on the quality of red dragon fruit juice were comprehensively evaluated through physicochemical properties, in vitro activity, metabolomics and flavoromics. The results indicate that the cloud stability of cold plasma (CP) treatment increased by 16.64%, the total polyphenol content increased by 13.76%, and its antioxidant capacity was higher than that of other treatments. Cold plasma significantly increased the content of L-tyrosine and affected the amino acid metabolic pathways of RDFJ, which can contribute to the total phenolic content of RDFJ and antioxidant activity. CP treatment effectively preserved the aroma components of RDFJ and decreased the content of harmful furan volatile compounds. The results suggest that cold plasma is a promising innovative non-thermal processing technique in RDFJ.