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Background: The Middle East and North Africa (MENA) region faces unique challenges in promoting physical activity and reducing sedentary behaviors, as the prevalence of insufficient physical activity is higher than the global average. Mobile technologies present a promising approach to delivering behavioral interventions; however, little is known about the effectiveness and user perspectives on these technologies in the MENA region., Objective: This study aims to evaluate the effectiveness of mobile interventions targeting physical activity and sedentary behaviors in the MENA region and explore users' perspectives on these interventions as well as any other outcomes that might influence users' adoption and use of mobile technologies (eg, appropriateness and cultural fit)., Methods: A systematic search of 5 databases (MEDLINE, Embase, CINAHL, Scopus, and Global Index Medicus) was performed. Any primary studies (participants of all ages regardless of medical condition) conducted in the MENA region that investigated the use of mobile technologies and reported any measures of physical activity, sedentary behaviors, or user perceptions were included. We conducted a narrative synthesis of all studies and a meta-analysis of randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs; quality assessment of the rest of the included studies was completed using the relevant Joanna Briggs Institute critical appraisal tools., Results: In total, 27 articles describing 22 interventions (n=10, 37% RCTs) and 4 (15%) nonexperimental studies were included (n=6141, 46% women). Half (11/22, 50%) of the interventions included mobile apps, whereas the other half examined SMS. The main app functions were goal setting and self-monitoring of activity, whereas SMS interventions were primarily used to deliver educational content. Users in experimental studies described several benefits of the interventions (eg, gaining knowledge and receiving reminders to be active). Engagement with the interventions was poorly reported; few studies (8/27, 30%) examined users' perspectives on the appropriateness or cultural fit of the interventions. Nonexperimental studies examined users' perspectives on mobile apps and fitness trackers, reporting several barriers to their use, such as perceived lack of usefulness, loss of interest, and technical issues. The meta-analysis of RCTs showed a positive effect of mobile interventions on physical activity outcomes (standardized mean difference=0.45, 95% CI 0.17-0.73); several sensitivity analyses showed similar results. The trim-and-fill method showed possible publication bias. Only 20% (2/10) of the RCTs measured sedentary behaviors; both reported positive changes., Conclusions: The use of mobile interventions for physical activity and sedentary behaviors in the MENA region is in its early stages, with preliminary evidence of effectiveness. Policy makers and researchers should invest in high-quality studies to evaluate long-term effectiveness, intervention engagement, and implementation outcomes, which can inform the design of culturally and socially appropriate interventions for countries in the MENA region., Trial Registration: PROSPERO CRD42023392699; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392699., (©Huong Ly Tong, Aroub Alnasser, Najim Z Alshahrani, Rowaedh A Bawaked, Reem AlAhmed, Reem F Alsukait, Severin Rakic, Volkan Cetinkaya, Hazzaa M Al-Hazzaa, Saleh A Alqahtani. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 19.03.2024.)