Background Lifestyle interventions to reduce weight and increase activity may preserve higher-order cognitive abilities in overweight/obese adults with type 2 diabetes (T2D). Methods Adults (N = 5,084) with T2D who enrolled in a randomized clinical trial of a 10-year intensive lifestyle intervention (ILI) compared with diabetes support and education were queried at baseline and repeatedly during follow-up for complaints about difficulties in memory, problem-solving, and decision-making abilities. Results For those without baseline complaints, assignment to ILI was associated with lower odds that complaints would emerge during follow-up for decision-making ability (odds ratio [OR]=0.851, [95% CI, 0.748,0.967], p=0.014), and, among individuals who were not obese, lower odds that complaints would emerge about problem-solving ability (OR=0.694 [0.510,0.946]). No cognitive benefits from ILI were seen for individuals with baseline complaints about cognitive abilities. ILI may have exacerbated the severity of complaints about problem-solving ability during follow-up among individuals with baseline complaints and cardiovascular disease (OR=2.949 [1.378,6.311]). Conclusions A long-term multidomain ILI may reduce the likelihood that complaints about difficulties in higher-order cognitive abilities will emerge in T2D adults without pre-existing complaints. Among those with pre-existing complaints, the ILI did not prevent increases in complaint severity.