Chronic Obstructive Pulmonary Disease (COPD) is a major global health problem. Among other conditions, it has been associated with chronic airway and lung parenchyma inflammation. At present, the available therapies are not capable of reducing the progression or suppressing inflammation associated to COPD. Therefore, there is a pressing need to find new treatments. Cigarette smoking (CS) is clearly the number one risk factor in the development of COPD since it causes oxidative stress and triggers inflammatory responses in the lungs of COPD patients. Numerous evidences indicate that oxidative stress plays a central role in the progression of the disease. Therefore, effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD. Historically, natural products (NPs) are the main source of potential drugs and their antioxidant potential has been widely recognized. Furthermore, various reports have suggested that NPs act as modulators of targets related to COPD, and some of them exert a multi-target mode of action. Among these multi-target NPs, some of the most promising are resveratrol, a potent antioxidant found in wine, and curcumin, found in turmeric. NPs with potential multi-target action have demonstrated anti-inflammatory, anticancer, cardio protective and neuroprotective properties and some of them have shown potential use in the treatment of chronic diseases featured by oxidative stress.