BackgroundSince the beginning of the COVID-19 pandemic, sanitary context and e-learning have greatly modified student lifestyles and led to deteriorations in their mental health. An increase in anxiety and depressive symptoms and sedentary behaviors, reduction in physical activity, and a stronger tendency to move toward unhealthy diet have been demonstrated. This finding highlights the need for innovative interventions to promote healthy lifestyle among students.ObjectiveThis research protocol aims to evaluate the effects of an intervention program on the lifestyle and psychological state of students.MethodsStudents from University of Nîmes were recruited and randomly assigned to 1 of 2 following conditions: an intervention group and a control group. Participants in the intervention group were engaged in an 8-week physical activity program. Prior to the start of the program, design-based innovative workshops were conducted with participants to ensure that the program was co-constructed by the users and met their specific needs. Students in the control group did not receive any intervention. For each group, measures of physical activity, sedentary time, anthropometric data, sleep, physical condition, and psychological variables (eg, anxiety, depression, motivation, body appreciation, perceived control, well-being) were conducted at baseline and 9 weeks later.ResultsA total of 110 participants were initially included. Reporting of the results is projected for the spring of 2022.ConclusionsIt is anticipated that this innovative intervention co-constructed by pairs will promote a healthier lifestyle and psychological health in students. There is every reason to believe that a mobilized co-construction approach is a promising strategy to limit unhealthy habits and promote physical activity while increasing motivation. The development and evaluation of interventions to address the specific needs of university students is essential and could be transferred to other vulnerable populations such as people with chronic diseases or older people.Trial RegistrationClinicalTrials.gov NCT05019482; https://clinicaltrials.gov/ct2/show/NCT05019482International Registered Report Identifier (IRRID)DERR1-10.2196/36429