This study aimed to examine the effect of a lifestyle intervention (LSI) on overweight or obese female university students. Participants: A total of 53 overweight or obese female college students participated. This study was conducted from May to December 2017 in Jeonbuk Province, South Korea. A quasi-experimental design using a non-equivalent control group pretest-posttest was used. The LSI consisted of providing health information, individual health counseling, lifestyle monitoring, and effective support based on the interaction model of client health behavior, which was implemented for 12 weeks. Significant group differences were found in health-promoting behavior, psychological distress, reproductive health, body weight, body fat, and triglyceride level among participants. LSIs are effective in improving health-promoting behavior, psychological distress, reproductive health, and body composition. Therefore, healthcare providers should develop and apply LSIs through interaction for overweight or obese female college students.