Ozone treatment is a non-thermal technology with promising applications in food processing. The objective of this study was to evaluate the effect of gaseous ozone at a concentration of 7.0 ± 2.4 g/L for 30 and 60 min of exposure, on some physicochemical characteristics (soluble solids content, pH, titratable acidity and color), bioactive compounds (vitamin C, total phenolics and carotenoids) and total antioxidant activity of Cantaloupe melon juice. The effectiveness of the ozone treatments in microbial survival was also assessed using Alicyclobacillus acidoterrestris spores as target spoilers of the juice (artificially inoculated). Some quality parameters were significantly affected by ozone treatments. The most relevant alterations were observed for color, vitamin C, carotenoids and total antioxidant activity. However, total phenolics content increased significantly in ozonized juices. Even though A. acidoterrestris spores reduced 2.22 ± 0.04 log cycles after 60 min of exposure, other quality related characteristics of the juice were modified. Industrial relevance: The actual consumers demand for high-quality food standards have launched research to alternative and milder non-thermal processes, which have gained increasing attention and importance in the fruit juice industries. Ideally, preservation and/or processing of foods should involve technologies that prevent undesirable microbial survival and minimize quality attributes changes and nutrient losses. Thermal treatments are conventionally used to attain such targets, however, the content and the biological activity of the most health-related compounds are dramatically reduced. In this context, and particularly for the beverages industries, ozone has been exploited due to their potential for inactivating spoilage and pathogenic microorganisms while being effective in overall quality retention of the products.