The study investigated the effect of sonication conditions on antioxidant activity of Hermetia illucens larvae meal protein hydrolysates. Three‐factor three‐level: pH (7–9), time (10–30 min), and temperature (25–55°C) were optimized. Box–Behnken's design was applied to optimize sonication treatment. Ferrous ion chelating activity (ICA), DPPH‐radical scavenging activity (DPPHRSA), Hydroxyl radical scavenging activity (HRSA), and cupric ion chelating activity (CCA) were considered as responses. Findings demonstrated that sonication preceding enzymolysis significantly impacted on ICA, DPPHRSA, HRSA, and CCA. ANOVA showed the determination coefficient (R2) were 0.98 (ICA), 0.99 (DPPHRSA), 0.98 (HRSA), and 0.88 (CCA); demonstrating that the models were reasonably fit with experimental results. Optimum sonication conditions were pH (9), time (29.84 min), and temperature (54.93°C). For these conditions, the experimental data obtained [ICA (37.84%), DPPHRSA (43.19%), HRSA (71.01%), and CCA (68.93%)] were consistent with predicted values, higher than control, and supported by protein subunits, fluorescence spectra and microstructure.