Focusing on adverse dietary exposures, this review examines whether physical activity can attenuate, reverse, or offset their associated health risks. Adverse dietary exposures and physical inactivity are both important modifiable factors in the development and progression of non-communicable diseases and premature mortality, but they are not simply interchangeable. Current epidemiological evidence suggests that higher levels of physical activity and cardiorespiratory fitness may attenuate the associations of poor diet quality, alcohol consumption, sugar-sweetened beverage intake, and other adverse dietary exposures with the development and progression of chronic diseases as well as premature mortality; among these, the evidence is relatively abundant for overall diet quality and alcohol consumption, whereas direct interaction evidence for ultra-processed foods, processed meat, and high-sodium diets remains limited. Physical activity may reduce individual susceptibility to some diet-related risks by improving energy balance, adiposity, insulin sensitivity, inflammation, vascular function, and cardiorespiratory fitness. It can attenuate some risks associated with adverse dietary exposures, but such risk regulation is not equivalent to the neutralization of biological hazards. Exposure-specific harms, including alcohol-related acetaldehyde toxicity and DNA damage, carcinogenic compounds from processed meat, sodium-related blood pressure load, addiction, or acute injury will not be eliminated by exercise. Therefore, public health recommendations should emphasize the simultaneous advancement of reducing adverse diet exposures and improving physical activity, rather than treating exercise as an “offset” for adverse dietary exposures.