Juice is a stable part of people’s diets worldwide, and its safety and quality are dependent on the effectiveness of processing technologies. Consumers are demanding clean labels and minimally processed food, driving the industry to explore options such as non-thermal processing technologies, such as high pressure processing (HPP), and natural antimicrobial compounds, such as natural glycolipids (NG). Chapters two and three investigate the synergistic effects of HPP and the NG against Alicyclobacillus acidoterrestris, a spore-forming spoilage bacterium responsible for off-odor development in apple juice. Findings demonstrate that the combined use of HPP at 600 MPa and 5 °C for 3 minutes and 50 ppm NG effectively inhibits both vegetative growth and spore outgrowth, supporting the potential for shelf-stable HPP juice products. Chapters four and five focus on Cryptosporidium parvum, a protozoan parasite responsible for apple juice outbreaks via contamination from dropped fruits. Current juice safety regulation requires the juice process to achieve at least 5-log reduction of C. parvum in apple juice; however, limited research exists on HPP’s efficacy against this protozoan pathogen. This dissertation reviews existing validation methods and presents new data using cell line infectivity assays, mRNA viability assays, RNA sequencing, and scanning electron microscopy to evaluate C. parvum inactivation. Results indicate that HPP can effectively reduce C. parvum infectivity through structural and membrane damage, offering insights for future validation protocols. Collectively, this work contributes to the development of scientifically grounded, non-thermal juice processing strategies that enhance microbial safety and product stability while aligning with consumer demand for minimally processed, high-quality juice products.