Per- and Poly-fluoroalkyl substances (PFASs) are among the substances that have been widely employed across the world due to their distinct features. These chemicals' great stability in the environment and capacity to be released from consumer goods have demonstrated their existence in all matrices. Additionally, the world's attention has been drawn to these substances' direct relation to human health in recent years. This research aimed to unravel the nexus of PFASs with obesity and endocrine disruption as a comprehensive review. Studies have shown that drinking water is the primary way in which humans are exposed to PFASs. As a result, it has become difficult to determine how drinking water is contaminated with these compounds and how their impacts affect human health. Through various routes, disruption of metabolic processes, and possible effects on the hypothalamus-pituitary-thyroid axis, these chemicals increase the incidence of obesity, particularly during crucial growth phases. Another negative health impact of PFASs is the disruption of the endocrine glands' function, which is crucial for controlling the body's physiological functions. This leads to alterations in hormone production. The effects of exposure to these substances include secondary hyperparathyroidism, non-alcoholic fatty liver, diabetes, cardiovascular illnesses, reproductive abnormalities, and infertility. Because of their characteristics, including the propensity to propagate through the food chain, accumulate and biomagnify, and ultimately pose a threat to human life, it is crucial to replace and remove these chemicals.