BackgroundAnxiety disorders and depression are prevalent disorders with high comorbidity, leading to greater chronicity and severity of symptoms. Given the accessibility to treatment issues, more evaluation is needed to assess the potential benefits of fully automated self-help transdiagnostic digital interventions. Innovating beyond the current transdiagnostic one-size-fits-all shared mechanistic approach may also lead to further improvements.ObjectiveThe primary objective of this study was to explore the preliminary effectiveness and acceptability of a new fully automated self-help biopsychosocial transdiagnostic digital intervention (Life Flex) aimed at treating anxiety and/or depression, as well as improving emotional regulation; emotional, social, and psychological well-being; optimism; and health-related quality of life.MethodsThis was a real-world pre-during-post-follow-up feasibility trial design evaluation of Life Flex. Participants were assessed at the preintervention time point (week 0), during intervention (weeks 3 and 5), at the postintervention time point (week 8), and at 1- and 3-month follow-ups (weeks 12 and 20, respectively).ResultsThe results provided early support for the Life Flex program in reducing anxiety (Generalized Anxiety Disorder 7), depression (Patient Health Questionnaire 9), psychological distress (Kessler 6), and emotional dysregulation (Difficulties in Emotional Regulation 36) and increasing emotional, social, and psychological well-being (Mental Health Continuum—Short Form); optimism (Revised Life Orientation Test); and health-related quality of life (EQ-5D-3L Utility Index and Health Rating; all false discovery rate [FDR]<.001). Large within-group treatment effect sizes (range |d|=0.82 to 1.33) were found for most variables from pre- to postintervention assessments and at the 1- and 3-month follow-up. The exceptions were medium treatment effect sizes for EQ-5D-3L Utility Index (range Cohend=−0.50 to −0.63) and optimism (range Cohend=−0.72 to −0.79) and small-to-medium treatment effect size change for EQ-5D-3L Health Rating (range Cohend=−0.34 to −0.58). Changes across all outcome variables were generally strongest for participants with preintervention clinical comorbid anxiety and depression presentations (range |d|=0.58 to 2.01) and weakest for participants presenting with nonclinical anxiety and/or depressive symptoms (|d|=0.05 to 0.84). Life Flex was rated as acceptable at the postintervention time point, and participants indicated that they enjoyed the transdiagnostic program and biological, wellness, and lifestyle-focused content and strategies.ConclusionsGiven the paucity of evidence on fully automated self-help transdiagnostic digital interventions for anxiety and/or depressive symptomatology and general treatment accessibility issues, this study provides preliminary support for biopsychosocial transdiagnostic interventions, such as Life Flex, as a promising future mental health service delivery gap filler. Following large-scale, randomized controlled trials, the potential benefits of fully automated self-help digital health programs, such as Life Flex, could be considerable.Trial RegistrationAustralian and New Zealand Clinical Trials Registry ACTRN12615000480583; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368007