Growing concern about food quality and safety has driven the search for natural food additives. Furthermore, maqui leaf residue (MLR), recovered from infusions that have long been part of traditional Chilean herbal medicine, still conserves a high content of phenolic compounds. The aim of this study was to optimize the ultrasound-assisted extraction (UAE) of phenolics from MLR and evaluate their potential effect on salmon preservation. The optimized parameters for UAE (6 min, MLR:Water = 1:30, and 70 W), obtained by using a Box-Behnken design, rendered the highest total phenolic content and antioxidant capacity. Furthermore, UAE showed a higher concentration of phenolic compounds compared to conventional extraction techniques, as evaluated by UPLC-ESI-MS/MS. The salmon with MLR had up to four times lower levels of thiobarbituric acid reactive substances, induced by ozonated water treatment, than the sample without this natural antioxidant. Moreover, MLR exhibited similar or superior effectiveness compared to synthetic antioxidants, such as butylated hydroxyanisole (BHA), 3,5-Di-tert-4butylhydroxytoluene (BHT). This study highlights the use of short-time aqueous ultrasound extraction as an environmentally friendly technology that allows the recovery of phenolic compounds from MLR, with potential application as a natural preservative that may replace or decrease the use of BHA and/or BHT.