The current perspective aimed to investigate the consequences of chronic exposure to alkylphenol xenobiotic (nonylphenol; NP) on humoral immune response, blood proteins, and stress indices as well as the immunological and pro/anti-apoptotic gene expression. In addition, this study assessed the potential ameliorative effect of common sage leaf powder (CSLP) against NP toxicity. A total of 240 mirror carp (Cyprinus carpio var specularis) were randomly distributed into four experimental groups with three replicates per group (20 fish/replicate) for 60 days: a control group, a group fed CSLP-supplemented diet (4 g/kg), a group exposed to NP (0.1 mg/L), and NP exposed group co-fed CSLP-supplemented diet. The exposure to NP at level 0.1 mg/L significantly (P < 0.05) decreased serum immune-biochemical biomarkers (lysozyme activity, complement-3, total protein, albumin, and globulin levels), with a marked increase in stress indicators (glucose and cholesterol) levels. On the molecular level, exposure to NP at level 0.1 mg/L induced a down-regulation of immune-related gene expression (inter leukin 1beta, toll-like receptor 7, interleukin 10, phosphoinositide-3-kinase regulatory subunit 3b(gamma), and nuclear factor kappa beta p65). The pro-apoptosis genes (Bcl-2 associated X-protein and cysteine-aspartic pro tease 3b) were boosted and the anti-apoptosis gene (B-cell lymphoma 2) was down-regulated by the exposure to NP. In addition, the expression of antioxidant (superoxide dismutase) and DNA repair (proliferating cell nuclear antigen) genes were disrupted. Conversely, dietary CSLP alleviated the alterations in the above-mentioned im mune-biochemical and stress response parameters in the NP-exposed group. It also restored the disturbance of immune, antioxidant, and apoptosis regulatory-associated genes. In conclusion, NP could consider an immu notoxin and apoptotic inducer in C. carpio var specularis. The CSLP is a successful dietary supplement in aquafeed for its palliative effects against NP toxicity.