Pursuit of physical activity goals often requires modifying plans, but research on these flexible processes is limited. Cognitive flexibility may heighten one’s likelihood of using flexible self-regulatory strategies (e.g., substitution), thereby increasing physical activity. This study used daily diary methodology to test the indirect effect of cognitive flexibility on physical activity via activity substitution. A sample of 128 college students (73% female, mean age 19.9) completed baseline measures and cognitive flexibility assessments, then logged physical activity daily for 2 weeks. Activity substitution was defined as adopting an alternate activity on a day another planned activity was unfulfilled. Controlling for baseline activity, intentions, and time, a multilevel mediation model revealed a significant indirect effect of cognitive flexibility on physical activity via activity substitution (b = 81.36, p = .041). Our results indicate that people with greater cognitive flexibility are more likely to use flexible self-regulation, leading to greater physical activity.