Lab animals such as mice and rats are widely used in toxicity research of food additive and pharmaceutics, despite the well-recognized research limitation such as the inability to simulate human neurological diseases, faster absorption of chemicals, big variations among species, and high cost when using a large number of animals. The Society of Toxicology's guidance now focuses on minimizing discomfort and distress of lab animals, finding alternative ways to reduce animal number, replacing animals with in vitro models, and complying to the animal welfare policies. The chicken embryonic model can be a better alternative to mice and rats because of its abundant availability and cost-effectiveness. It can be studied in both laboratory and natural environment, with easy manipulation in ovo or in vivo. The objective of this review paper is to evaluate the use of chicken embryonic model in toxicity evaluation for endocrine-disrupting chemicals (EDCs) and nanoparticles (NPs) by different end points to determine more comprehensive toxic responses. The end points include chicken embryonic mortality and hatchability, developmental malformation analysis, hormonal imbalance, physiological changes in endocrine organs, and antiangiogenesis. Major research methodologies using chicken embryos are also summarized to demonstrate their versatile practice and valuable application in modern toxicity evaluation of EDCs and NPs.