The current study was conducted to evaluate whether gamma (γ)‐irradiation improves the efficacy of defatted Hermetia illucens larvae (HIL) meal as the fishmeal protein substitute in Litopenaeus vannamei . The reference diet (diet R) contained 400 g/kg fishmeal, while two experimental diets replaced 50% of fishmeal with either nonirradiated (diet HIL) or γ‐irradiated defatted HIL meal (diet HIL5). Compared to group R, both average final body weight (FBW) and weight gain exhibited an increasing trend with the inclusion of defatted HIL meal, particularly with γ‐irradiated HIL. Lower feed intake and feed conversion ratio (FCR) while increased retention efficiencies of carbon (CRE), nitrogen, and phosphorus were observed in groups HIL and HIL5 than the R group. Additionally, with the incorporation of either γ‐irradiated or nonirradiated defatted HIL meal, significantly decreased malondialdehyde (MDA), carbon waste, nitrogen waste, phosphorus waste, relative usage of fishmeal and fish oil, and the ratio of fish‐in to fish‐out, whereas increased economic conversion ratio, economic profitability index, and profitability were observed compared to the shrimp fed a fishmeal‐based diet. Microbial analysis revealed a trend toward increased Pseudomonadota ( Ruegeria and Vibrio ) and decreased Bacillota ( Streptococcus ), though no statistical differences in alpha diversity or microbial community structure were observed. No adverse effects were detected in body components, digestive enzyme activities, or hepatopancreatic antioxidant capacity (AOC). These results demonstrate that γ‐irradiated defatted HIL meal can effectively replace 50% of dietary fishmeal (from 400 to 200 g/kg) without compromising growth performance, antioxidant status, or intestinal health in L. vannamei . Moreover, this substitution improves feed utilization, economic viability, and environmental sustainability by reducing waste output and fishery dependence.