Objective <p>Given that the potential joint effects of physical activity (PA) and dietary inflammatory index (DII) on diabetic kidney disease (DKD) remain unclear, this study aimed to investigate both the independent and combined associations between DII, PA, and DKD in U.S. adults, thereby providing theoretical evidence for the synergistic impact of lifestyle factors on DKD.</p> Methods <p>Data were extracted from the National Health and Nutrition Examination Survey database between 2009 and 2018. Weighted multivariable logistic regression models evaluated the independent and combined associations between PA, DII, and DKD. The interaction between PA and DII was assessed. Subgroup analyses were conducted by smoking status, sex, hypertension, and age.</p> Results <p>A total of 3680 individuals with diabetes were included. Both inactive PA (OR = 1.330, 95% CI: 1.091–1.662) and a higher DII (OR = 1.353, 95% CI: 1.072–1.708) were associated with a higher DKD prevalence. Individuals with inactive PA and higher DII were associated with the highest OR (OR = 1.809, 95% CI: 1.380–2.370). A significant synergistic interaction between PA and DII was observed. When PA was active, a higher DII was still associated with an increased DKD prevalence (OR = 1.524, 95% CI: 1.058–2.196). Subgroup analyses revealed significant associations in males (OR = 1.850, 95% CI: 1.170–2.925), adults aged ≥ 65 years (OR = 2.012, 95% CI: 1.090–3.712), never smokers (OR = 1.771, 95% CI: 1.096–2.861), former smokers (OR = 1.914, 95% CI: 1.116–3.141), and hypertensive individuals (OR = 1.474, 95% CI: 1.016–2.139).</p> Conclusion <p>Inactive PA and a high DII were independently and jointly associated with an elevated DKD prevalence. Combining increased PA with a low-inflammatory diet may be more effective in reducing the likelihood of developing DKD than focusing on either factor alone, particularly among men, older adults, never-smokers, former smokers, and patients with hypertension.</p>