Abstract: This paper provides a systematic overview of the potential disruptive effects of per- and polyfluoroalkyl substances (PFASs) on thyroid hormone levels and the underlying mechanisms. PFASs, as a class of synthetic substances that are highly stable and not easily degraded, have been widely used in various industrial and consumer products. Due to their persistence and ubiquity, PFASs are frequently detected in the environment, and can enter the human body via the food chain, water, and air, thus posing a potential threat to human health. Exposure to PFASs has been shown to have the potential to interfere with the normal levels of thyroid hormones, thereby adversely affecting their secretion and metabolism. The correlation between PFASs exposure and thyroid hormone fluctuations has been demonstrated in both population-based epidemiological studies and animal studies. In vitro studies have further clarified that PFASs exposure may disrupt thyroid hormone levels by interfering with the feedback regulation of the hypothalamic-pituitary-thyroid axis, altering the expression of key transcription factors, affecting the synthesis and metabolism of thyroid hormone-related proteins and enzymes, and inducing toxicity to thyroid cells, ultimately impairing thyroid function and health. Considering the potential disruptive effects of PFASs on thyroid hormone levels and their widespread presence in the environment and the human body, this paper highlights the urgency of strengthening the regulation of PFASs use and release as well as the urgent need for more in-depth studies to comprehensively unravel their potential impact on human health.