Objective To identify latent self-disclosure profiles among adolescents with depression, to explore their associations with social isolation, and to examine the mediating role of depressive mood. Methods A cross-sectional study was conducted among 388 adolescent patients diagnosed with depression. Participants completed a general information questionnaire, the Distress Disclosure Index (DDI), the Patient Health Questionnaire for Adolescents (PHQ-A), and the General Alienation Scale (GAS). Latent profile analysis (LPA) was used to identify self-disclosure subgroups. Mediation analysis was conducted using the Bootstrap method. Results Three distinct self-disclosure profiles were identified: the self-concealing group (26.0%), the peer-disclosing group (41.5%), and the multi-target disclosing group (32.5%). Significant differences in social isolation scores were found across the three groups (P<0.05), with the self-concealing group scoring the highest. Mediation effect analysis revealed that, compared to the multi-target disclosing group, both the peer-disclosing group and self-concealing group had higher level of social alienation. Moreover, through depressive mood, the latter 2 groups impacted social alienation, with the self-concealing group demonstrating a more pronounced effect than thepeer-disclosing group (all P<0.05). Conclusion Adolescents with depression exhibit significant heterogeneity in self-disclosure patterns. Medical staff should tailor intervention strategies based on individual disclosure profiles. Enhancing self-disclosure abilities may help reduce depressive mood and in turn, alleviate the level of social isolation.