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Owing to its poor solubility, the applicability of dihydromyricetin (DMY) is limited in various biomedical applications. To overcome this issue, nano-sized DMY particles (DMY NPs) were fabricated using the supercritical antisolvent (SAS) approach for improving the bioavailability of DMY. Initially, the experimental conditions were optimized such as temperature of 45 °C, pressure of 8 MPa, and DMY solution flow rate of 0.5 mL/min, resulting in the DMY particles at a mean particle size of 169.1 ± 23.7 nm. Further, the physicochemical characteristics of the resultant DMY NPs were evaluated using various characterization techniques. The DMY NPs with reduced particle size and improved dissolution rate resulted in improved anticancer, antibacterial, and biofilm inhibition efficacies, comparable to that of unprocessed DMY. Together, the designed DMY NPs using the SAS process have great potential in food and …