Homeless girls suffer labour and sexual exploitation, abuse, discrimination and social exclusion at a higher rate than the rest of the population. However, worldwide information on homeless girls and intervention programmes for this group are scarce. This study examined the preliminary efficacy of a brief cognitive behavioural group therapy tailored to Mexican homeless girls. The intervention targeted subjective well-being and these determinants: symptoms of anxiety, symptoms of depression, assertive behaviours and functional emotion regulation skills. Results revealed statistically significant differences in symptoms of anxiety and depression, assertiveness, emotion regulation strategies and subjective well-being with treatment effects that ranged from moderate to large. Symptoms of anxiety and depression, and dysfunctional emotion regulation strategies decreased. Assertive skills, functional emotion regulation strategies, and subjective well-being increased. Outcomes were clinically relevant. At 2-month follow-up, participants showed improvement from pre-treatment on all measures. The current study provides unique findings in terms of a promising preliminary intervention that helps restore homeless girls to a healthier social/emotional developmental path especially in the context of Latin American cities. As a result, the clinical implications of this research highlight the urgent need to design effective interventions based on the observed characteristics and identified needs among homeless girls.