This study investigated the effect of ultrasound pretreatment (UAE) on the extraction of astaxanthin-rich lipid extract from the by-product of the Jinga shrimp (Metapenaeus affinis). The effect of solvent type (hexane, ethanol, and hexane/ethanol mixture) and extraction conditions (time and power of ultrasound waves) on the extraction efficiency, astaxanthin content, antioxidant activity, and oxidative stability of the extract was evaluated. The samples were subjected to ultrasound treatment for 5 to 15 minutes and a power of 20 to 100 watts using response surface methodology (RSM). Lipid extraction was performed by the Soxhlet method and different solvents. Antioxidant activity was measured by DPPH assay, and oxidative stability was measured by peroxide (PV) and thiobarbituric acid reactive substances (TBARS) indices. Statistical analysis showed that the quadratic central composite design (CCD) model was able to predict the extraction efficiency. The optimal conditions were obtained at 7 minutes and 100 watts (power density: 2.5 W/L). The highest lipid yield (0.33 g/100 g dry weight) and the highest astaxanthin concentration (843.63 μg/100 g) were obtained with ultrasound pretreatment and hexane/ethanol mixed solvent. This treatment also showed the highest DPPH free radical scavenging activity (77%) and the lowest peroxide and TBARS indices. The results showed that ultrasound pretreatment with hexane/ethanol dual solvent significantly increased the extraction yield, astaxanthin concentration, and antioxidant activity of the extract. Therefore, UAE, as a green and efficient technology, can be an effective solution for recovering high-value-added bioactive compounds from shrimp by-product and improving the economic and environmental efficiency of aquaculture industries.