Background: Quality of life (QoL) is an important outcome in the management of children with asthma. Mobile Health (m-Health) and Therapeutic Education Programs (TEPs) are increasingly recognized as essential components of pediatric asthma management to improve disease outcomes. Objective: To evaluate the effect of an education program (MyTherapeutic Education Program, MyTEP) that couples multidisciplinary TEP intervention with an m-Health Program (mHP) in improving QoL in asthmatic children. Methods: This single-center study employed a nonblinded randomized clinical trial design. Italian-speaking children (6–11 years) with mild-moderate asthma were eligible for participation. Participants were randomly paired 1:1 with a control group that received mHP (smartphone app) or an intervention group that received MyTEP (TEP plus a smartphone app). Patients were followed up for 3 months. Descriptive statistics, Least Square (LS) mean change and Generalized Linear Mixed model were used for analysis. Results: Fifty patients were enrolled. The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) score improved in both MyTEP (p = 0.014) and mHP (p = 0.046) with the minimally clinically significant difference of ⩾0.5 points reached in 23% of MyTEP and in 16% of mHP. Changes in PAQLQ scores were significantly greater in MyTEP than in mHP (LS mean difference: 0.269 p = 0.05). PAQLQ score was: positively associated with MyTEP (p = 0.023) and study time (p = 0.002); and inversely associated with current passive smoke exposure (p = 0.003). Conclusion: Despite the small sample size and short observation period, this study demonstrated that implementing a multidisciplinary TEP with an m-Health program results in gains in QoL of children with asthma.