Abstract Background Digital interventions are typically evaluated by their effectiveness and engagement, while the characteristics of patients who perceive them to be attractive have remained poorly understood. This challenges user-centered intervention development but also presents an avenue to improve intervention efficacy and engagement. Our objective was to characterize people to whom game-based interventions appeal to with a focus on their mental health backgrounds and prior digital game experiences. Methods We performed a sequential mixed methods study with adults suffering from major depressive disorder (MDD) who participated in a randomized controlled clinical trial studying the effectiveness of a game-based digital intervention for depression. First, randomly chosen participants were interviewed (N = 22), and the transcribed data were analyzed inductively. Then, focusing on the themes established through the interview data, we triangulated the findings using complementary questionnaire data (N = 445). Results The interview data yielded four themes that we illuminated with quantified questionnaire data. (T1) The participants had enduring and diverse psychiatric symptomology: 73% had been diagnosed with a comorbid disorder in addition to depression. (T2) Participants had received at least some treatments that had not led to full remission of depression. 92% currently received therapeutic support, psychiatric medication, or both. (T3) Many participants had close relationships with digital gaming and played actively: on average, for 13 h a week on various gaming platforms and in various genres. (T4) Some participants used gaming to manage their psychiatric symptoms, and 76% found that playing helped them feel better. Conclusions Identifying and characterizing people attracted to game-based therapeutic interventions can catalyze intervention development and improve their efficacy. We found that game-based interventions have appealing potential across diverse psychiatric symptoms and for people with prior or existing treatments. Game-based interventions may appeal particularly to active players and offer a promising alternative to the self-treatment usage of entertainment games.