BackgroundOverweight and obesity lead to a range of noncommunicable diseases (NCDs), such as type 2 diabetes, cardiovascular disease, and stroke. Physical activity (PA) is an important lifestyle behavior for controlling body weight. Dietary inflammatory index (DII), which is associated with systemic inflammatory markers, is used to evaluate the potential of dietary inflammation. This is the first study to investigate the independent and joint associations of PA and DII with the risk of overweight/obesity among US adults.MethodsParticipants and data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007–2018, which is designed to examine the health and nutritional status of the non-institutionalized US population by a complex, multi-stage, probability sampling design.ResultsA total of 10723 US adults were selected. Physically active participants had lower overweight/obesity risk (total-time PA: OR = 0.756, 95% CI: 0.669–0.855; leisure-time PA: OR = 0.723, 95% CI: 0.643–0.813; and walk/bicycle-time PA: OR = 0.748, 95% CI: 0.639–0.875); however, those with work-time PA showed no significant association between PA and overweight/obesity. Compared with participants in the lowest DII group (Q1), those in the other three groups had high risks of overweight/obesity (Q2: OR = 1.218, 95% CI: 1.054–1.409; Q3: OR = 1.452, 95% CI: 1.245–1.693; Q4: OR = 1.763, 95% CI: 1.495–2.079). In joint analyses, PA was not eligible for reducing risks of weight/obesity if far more pro-inflammatory diet (Q4 of DII = 2.949–5.502) was taken in (total-time PA: OR = 1.725, 95% CI: 1.420–2.097; leisure-time PA: OR = 1.627, 95% CI: 1.258–2.105; walk/bicycle-time PA: OR = 1.583, 95% CI: 1.074–2.332; and work-time PA: OR = 1.919, 95% CI: 1.493–2.467).ConclusionsMore leisure-time PA and walk/bicycle-time PA are associated with lower risk of overweight/obesity, and higher DII is associated with higher risk of overweight/obesity. In addition, higher DII impacts overweight/obesity substantially: once the DII score reached Q4, there is still risks of overweight/obesity even if PA is performed.Supplementary informationThe online version contains supplementary material available athttps://doi.org/10.1265/ehpm.23-00016.