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<h4>Objective</h4> The use of mobile health (mHealth)-based interventions for the prevention of alcohol and other psychoactive substances use is an emerging practice for which new evidence is required. This study evaluated the feasibility and acceptability of a mHealth-based peer mentoring tool for early screening, brief intervention, and referral of students who abuse alcohol and other psychoactive substances. It compared the implementation of a mHealth-delivered intervention to the paper-based practice that is the standard at the University of Nairobi. <h4>Methods</h4> A quasi-experimental study using purposive sampling was used to select a cohort of n = 100 (51 experimental, 49 control) first-year student peer mentors on two campuses of the University of Nairobi in Kenya. Data were collected on the mentors’ sociodemographic characteristics as well as the feasibility and acceptability of the interventions by way of, the magnitude of reach, feedback to investigators, referral of cases, and perceived ease of use. <h4>Results</h4> The mHealth-based peer mentoring tool scored high with 100% of users rating it as feasible and acceptable. Among the two study cohorts, there were no differences in the acceptability of the peer mentoring intervention. When comparing the feasibility of the peer mentoring practice, actual use of the interventions, and intervention reach, the mHealth-based cohort mentored four mentees for every one mentored by the standard practice cohort. <h4>Conclusion</h4> The mHealth-based peer mentoring tool had high feasibility and acceptability among student peer mentors. The intervention provided evidence for the need to expand the availability of screening services for alcohol and other psychoactive substances use among students in the university and promote the appropriate management practices within and outside the university. Author summary Given the documented prevalence of harmful alcohol and other psychoactive substances use among young adults, the need for innovative ways to communicate behaviour change is urgent. The harmful use of psychoactive substances has a myriad of negative consequences for young adults both in the short term and long term. These eventually lead to poor life outcomes including loss of lives. Currently, there is a need for more evidence on the feasibility and acceptability of mHealth-based interventions for the prevention of the harmful use of psychoactive substances among young adults. This study adds to the body of evidence about efficacious measures for the prevention of the harmful use of alcohol and other substances among young adults. It is relevant in providing data on the feasibility and acceptability of mHealth-based peer mentoring in a university setting. Given the limited evidence of the effectiveness of mHealth-based interventions in Africa, this study adds evidence to this important but emerging practice. Finally, this study contributes to the achievement of the Global Sustainable Development Goals, specifically strengthening the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.