To our knowledge, limited information is available on the use of Zanthoxylum piperitum (ZP) and Z. ailanthoides (ZA) as dietary additives in shrimp; therefore, this study evaluated their effects on the physiological responses of Penaeus vannamei. Experimental diets were prepared by supplementing a basal diet with 0.5% or 1.0% ZP and ZA extract powders and fed to shrimp for 5 weeks. ZA supplementation significantly increased final body weight and weight gain, whereas both ZP and ZA diets significantly increased specific growth rate. ZP supplementation elevated key immune and antioxidant enzymes, including phenoloxidase and glutathione peroxidase, while ZA induced broader activation of innate immune and antioxidant responses. During Vibrio parahaemolyticus challenge, no significant differences in cumulative survival were observed among treatments, although PCR detection patterns and histological observations varied between ZP- and ZA-fed shrimp and the control group. These findings suggest that dietary Zanthoxylum supplementation may influence shrimp physiological responses, potentially by modulating immune and antioxidant systems. Overall, the results suggest the potential use of Zanthoxylum spp. as phytogenic feed additives for shrimp aquaculture.