Orange juice is the second most commonly consumed juice worldwide. However, its quality is deteriorated because pectin methyl esterase (PME), a thermostable enzyme. In this study, orange juice was processed by hydrodynamic cavitation (HC) at 4 bar pressure with varying temperatures (40℃–70℃) and process time (0–8 min). pH and TSS of the juice remained stable during HC processing. A decreased flow behavior index and increased flow consistency index was observed along with sedimentation index, indicating the effectiveness of HC in modifying the physical stability of juice. More retention of vitamin-C, phenolics, and antioxidants was observed in HC-processed juice compared with unprocessed; however, degradation was recorded at higher temperature. Maximum PME inactivation (65%) was observed at 70℃ for 8 min. Microbial inactivation at lower temperatures and time was achieved. Based on this research, it can be concluded that HC could be used as a potential liquid food-processing technique for improving the physicochemical and nutritional quality of orange juice. Practical applications: Hydrodynamic cavitation (HC) is an upcoming novel nonthermal processing used for improving the physicochemical, nutritional, and microbial quality of fruit juices. HC is advantageous over other methods because of its low capital cost, reduced time, high efficiency, and lower temperature that help in retention of bioactives in foods. HC also causes inactivation of enzymes and microorganisms, thus improving quality and safety of final product. This novel processing is not yet being explored much and there is huge scope for its application in preservation and processing of different fruit juices and other liquid foods (milk, cereal drinks etc.).