Electronic mentoring (e-mentoring), the integration of digital technology in mentoring relationships, has recently grown in popularity; however, the effectiveness of e-mentoring in addressing youth health has not been synthesized to date. The current study synthesizes the literature on e-mentoring to affect the health and well-being of youth (10–24 years) through a systematic review and evidence quality assessment. A total of 833 records were identified, of which 14 met eligibility criteria (published in English since 1995, targeted youth health and/or youth with health issues, and communication was entirely digital or combined with in-person interaction). The results showed that the majority of health-focused e-mentoring studies were conducted with young people with existing health conditions rather than on the use of e-mentoring to promote overall health and wellness. The included programs focused largely on bringing mentoring to youth subpopulations that may be challenged by in-person models. Quality assessments of the included studies showed that the strength of the evidence is mediocre. The findings suggest that e-mentoring has the potential to reach youth with unique health concerns and to promote independent management of health conditions as youth transition to adulthood; however, more rigorous evaluation of e-mentoring programs with larger sample sizes is needed.