This study assessed the efficacy of a bivalent IBV vaccination (H120/D274) against GI-23 (variant II) and the antiviral and immunostimulatory properties of dietary Nigella sativa plus β-glucan (NSG). A total of 186 one-day-old broiler chicks were used as follows: 1st group (n=42) received IBV vaccine (prime: 7- and post: 14- day of age) (VAX), 2nd group (n=42) received the additive without vaccination (NSG), 3rd group (n=42) received both the vaccine and additive (VAX-NSG), and 4th group (n=60) received neither vaccine nor additive (CTRL). The 4th group was subdivided on the challenging day to negative (CTRL-N) and positive (CTRL-P) control subgroups. All groups except CTRL-N were challenged via naso/ocular route with IBV Variant II at 14 days post 2nd vaccination (PV). Clinical protection, antibody titers, cytokine expression, immune organ indices, viral shedding, and renal and tracheal histopathological lesions were evaluated. Body weight loss% at 1-week post-challenge (pc) in VAX, NSG, and VAX-NSG was 28.47%, 31.28%, and 23.54%, respectively, compared to CTRL-P (43.72 %) (P<0.05). Remarkably, NSG group showed milder tracheal and renal histopathological lesions than VAX group at 3 and 7 dpc, while VAX-NSG group displayed normal histology. Oropharyngeal IBV shedding was successfully reduced by the vaccination regimen; the VAX-NSG group showed the lowest level (P<0.05). Splenic IL-6 and TNF-α mRNA expression was upregulated at 3- and 7-dpc in CTRL-P birds (P<0.05). They were significantly downregulated in VAX-NSG, VAX, and NSG groups (P<0.05). At 7 dpc, IBV reduced the CTRL-P group's bursa, thymus, and spleen indices (P<0.05) that were significantly reversed in other challenged groups. VAX, NSG, and VAX-NSG groups induced higher lacrimal IgA titers than the control (P<0.05) at weekly intervals PV; while pc, they were lower than CTRL-P (P<0.05). However, serum IgG titers were higher in the VAX group than VAX-NSG group PV, and the opposite was observed at 7 and 10 dpc (P<0.05). Conclusion, the combination of dietary NSG with the heterologous IBV vaccine (H120/D274) showed synergistic effects to stop variant II viral shedding by the 10th dpc, increase anti-inflammatory effects, prevent renal and tracheal histopathological lesions, and significantly reduce body weight loss post challenge.