Cigarette smoke (CS) is likely the most common preventable cause of human morbidity and mortality worldwide. Consequently, inexpensive interventional strategies for preventing CS-related diseases would positively impact health systems. Inhaled CS is a powerful inflammatory stimulus and produces a shift in the normal balance between antioxidants and oxidants, inducing oxidative stress in both the respiratory system and throughout the body. This enduring and systemic pro-oxidative state within the body is reflected by increased levels of oxidative stress and inflammation biomarkers seen in smokers. Smokers might benefit from consuming antioxidant supplements, or a diet rich in fruit and vegetables, which can reduce the CS-related oxidative stress. This review provides an overview of the plasma profile of antioxidants observable in smokers and examines the heterogeneous literature to elucidate and discuss the effectiveness of interventional strategies based on antioxidant supplements or an antioxidant-rich diet to improve the health of smokers. An antioxidant-rich diet can provide an easy-to-implement and cost-effective preventative strategy to reduce the risk of CS-related diseases, thus being one of the simplest ways for smokers to stay in good health for as long as possible. The health benefits attributable to the intake of antioxidants have been observed predominantly when these have been consumed within their natural food matrices in an optimal antioxidant-rich diet, while these preventive effects are rarely achieved with the intake of individual antioxidants, even at high doses.