School transitions are labeled as challenging events in students’ academic paths likely to affect students’ development and engagement in school negatively. Grounded on extant research advocating the need to act preventively, school-based mentoring programs emerge as responses suited to provide students with developmental and instructional support during school transitions. Using a multivariate mixed-effects model for repeated measures quasi-experimental design, the present study assessed the effectiveness of a 12-session group mentoring program designed to promote fifth-grade students’ self-regulation, school engagement, and goal setting during their first school transition. Participants were 330 fifth graders in four schools randomly assigned to treatment or control conditions. Students’ self-reported measures were collected in four moments. Data were analyzed using a multivariate mixed-effects model for repeated measures analyses with two covariates (age and gender) and considering the students’ level of prior mathematics knowledge. Results indicated that participating in the group mentoring program led to improvements in all dependent variables. The effect size found was large considering all dependent variables simultaneously. However, when considered individually, the effect sizes were medium, small, or null, depending on the dependent variable. Lastly, and contrary to expectations, the effectiveness of our program was not influenced by students’ level of prior mathematics knowledge. The relevance of group mentoring programs in addressing students’ engagement and self-regulation needs is discussed. Future research and educational implications for designing mentoring programs are provided.