This study determined the optimal pressure and time conditions for the high pressure processing (HPP) of a lemongrass-lime mixed beverage. The physicochemical and microbiological characteristics, bioactive compounds, and antioxidant activity of the beverage treated under the optimal HPP conditions were evaluated immediately after processing and during 8 weeks of storage at 4 °C, compared to untreated (control) and thermally pasteurized beverages. HPP at 250 MPa for 1 min at 25 °C ensured microbiological safety, according to inactivation tests with Listeria innocua as the target microorganism, without significant losses of vitamin C and phenolic compounds. Immediately after processing, the HPP treated beverage retained its original bioactive compounds content and showed physicochemical characteristics that were closer to the untreated control compared with the thermally pasteurized beverage. In addition, HPP provided microbiological quality and improved the shelf life of the beverage, demonstrating that it represents a reliable alternative to thermal treatment of lemongrass-lime mixed beverages.