Introduction: This study zoomed into the relation between self-regulation, resilience and quality of life (QOL) within a mixed psychiatric sample of patients with Dual-Diagnosis (DD) or an Autism spectrum disorder (ASD). Method: Patients with DD or ASD participated and healthy control (HC) data were present. The Barkley Deficits in Executive Functioning Scale (BDEFS), Shortened Temperament and Character Inventory and Manchester Short Assessment of Quality of Life were administered. Results: The BDEFS revealed more executive problem reporting by DD or ASD patients than by HC. Both patient groups revealed that, the more problems were reported in executive self-regulation (like self-motivation, problem-solving), the lower QOL was experienced. The resilience aspect of self-directedness (goal-directed, responsible attitude) was positively related to higher QOL and to lesser experience of self-motivational and problem-solving problems. But, the more harm-avoidant, the lesser one was self-directed and the more self-motivational and problem-solving problems were reported. Discussion: Self-regulation and harm-avoidance problems were related to lower QOL in DD and ASD. Self-directedness, executive self-motivation and problem-solving predicted higher QOL. Treatment focus on self-directedness, executive self-regulation and resilience is recommended.