Stress in aquaculture can trigger maladaptive physiological responses that weaken immunity and increase pathogen susceptibility, ultimately contributing to disease outbreaks. Catfish occupy an important position in fish immunology research, as their innate immune system is particularly strong and supported by an increasingly well-characterized genomic framework, making them an ideal model to study immune regulation. To explore sustainable strategies for improving fish immunity and welfare, a recent study investigated the effects of five phytogenic nutraceuticals (Enviro QS, Syrena Boost, Fresta Protect, Actifor Protect, and Actifor Power) on immune-related gene expression in hybrid catfish (Ictalurus punctatus × I. furcatus). Fish were fed nutraceutical-supplemented diets for 49 days, and intestinal tissues were analyzed by quantitative PCR targeting the cytokines il1b, il8, il10, and tnfa. Results demonstrated consistent upregulation of all immune genes across treatment groups compared to the control. Notably, Fresta Protect induced the strongest overall responses, with the highest expression of il1b, il10, and tnfa. The expression of il-8 was most elevated in Actifor Protect, while the Syrena Boost showed comparatively lower il-8 expression. These findings provide molecular evidence that phytogenic nutraceuticals modulate pro- and anti-inflammatory pathways in hybrid catfish, enhancing immune readiness at the genetic level. These results support the potential of nutraceutical supplementation as a bio-safe alternative to antimicrobials, contributing to the sustainability and resilience of catfish aquaculture.