This cohort-controlled trial examined whether the 12-session Grit Wellbeing and Self-regulation Program enhanced the treatment outcomes of young people accessing residential alcohol and other drug (AOD) treatment. Grit focuses on increasing wellbeing and reducing substance use and mental health problems by building self-regulation skills, strengths, social connections, and health behaviours. Participants were 194 (66% male, Mage 27.40) young people (aged 18–35 years) accessing a six-week residential treatment program for substance use. Participants received standard treatment, or standard treatment plus Grit (two sessions/week for six weeks). The primary outcome was substance use, measured as: (i) global substance use and (ii) alcohol, methamphetamine, and cannabis use involvement. Secondary outcomes included wellbeing, depression, anxiety, and vocational engagement. Participants were assessed at baseline, and 6-weeks (secondary outcomes only), 3-months, 6-months, and 12-months post-program enrolment. Results revealed that both groups showed a significant improvement in all outcomes at three months, and improvements were maintained at 6- and 12-month follow-ups. The Grit group had a larger reduction in methamphetamine and cannabis use involvement compared to the control group. This study presents promising evidence that a six-week residential program can achieve improvements in AOD use, depression, anxiety, wellbeing and vocational engagement. Further, targeting self-regulation may enhance such programs.