BACKGROUND AND AIMS: The success of every new technology depends on numerous factors, including specialists' knowledge and perceptions of the concept, acquired attitude skills, and work environments. This systematic review aimed to examine medical students' knowledge, attitudes, and perceptions of telemedicine. METHODS: Studies were obtained from the PubMed, Embase, Scopus, and Web of Science databases on June 9, 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Cross-sectional studies that examined medical students' knowledge, attitude, and perceptions of telemedicine approaches were considered inclusion criteria. Titles and abstracts were independently screened based on eligibility criteria. Articles that did not meet the inclusion criteria were excluded from this review. After that, the complete texts were retrieved and screened by two separate researchers based on the eligibility criteria. Disputes were resolved by discussion. The same checklist was used for data extraction. To assess the quality of the studies entering this study, the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross-sectional studies was used. RESULTS: In total, 10 eligible articles were found through this review. The sample size of the studies ranged from 60 to 3312 participants, or 6172 participants on the whole. The medical students' attitudes toward telemedicine were evaluated in eight included studies. Many of these studies (seven cases) reported positive and promising perspectives on telemedicine. However, in one study, participants revealed moderate attitudes toward online health information and online health experience sharing ( < 0.05). Students' knowledge of the telemedicine approach was evaluated in eight included studies. Many of these studies (five cases) reported that students possessed an extensively poor knowledge of telemedicine's uses. In three other studies, two reported moderate and one disclosed desirable levels of students' knowledge. All the included studies attributed medical students' poor knowledge to the lack of, and thus failure of, educational courses in this field. CONCLUSION: The evidence obtained from this review reveals that medical students possess positive and promising attitudes toward telemedicine technology for education, treatment, and care. However, their knowledge levels were extremely insufficient, and many had not passed any educational courses in this respect. Such results can foreground the health and education policymakers' obligations for planning, training, and empowering digital health and telemedicine literacy among medical students as the primary players in social health.