Introduction:
Newcastle Disease (ND) is a highly contagious viral infection that continues to cause significant mortality, production losses, and trade restrictions in poultry worldwide. Despite widespread vaccination, outbreaks persist due to the emergence of more virulent Newcastle Disease Virus (NDV) strains and reduced vaccine efficacy under field conditions. Complementary antiviral strategies are increasingly recognized as a necessary addition to vaccination programs.

Methods:
A comprehensive literature review was conducted using databases including PubMed, Web of Science, and Scopus. Studies published in English up to 2025 were screened for evidence on synthetic antivirals, plant-derived compounds, immunomodulators, and supportive agents against NDV. Both in vitro and in vivo studies were evaluated, with a focus on antiviral efficacy, safety, cost, and practical field applicability.

Results:
Synthetic antivirals, such as ribavirin and favipiravir, demonstrated moderate efficacy in controlled laboratory studies but are limited by high cost, toxicity concerns, and regulatory restrictions in poultry. Plant-based compounds, notably Curcuma longa (turmeric), Azadirachta indica (neem), and Allium sativum (garlic), showed promising antiviral and immunostimulatory effects with better accessibility and safety profiles. Immunomodulators, including interferons, and supportive agents such as vitamins and probiotics, enhanced host resistance. However, most evidence comes from in vitro studies, with a shortage of well-designed in vivo and field trials.

Conclusions:
The literature supports integrating validated plant-based antivirals and immunomodulators with vaccination to create a more robust and sustainable ND control strategy. Priority research should focus on large-scale in vivo and field evaluations to confirm efficacy, safety, and cost-effectiveness under commercial conditions. Such integration could significantly reduce ND-related losses and improve poultry health management.