Objective This study aimed to investigate the differences in perception of depressive symptoms, loneliness, and social support from friends between young adults with and without Non-Suicidal Self-Injury (NSSI) engagement in the past year. Moreover, we proposed a model analyzing the moderating effect of NSSI engagement in the mediating role of perceived social support from friends between depressive symptoms and loneliness.Method A total of 320 young adults with a history of NSSI (aged 18–35 years) were assigned to two groups: NSSI engagement within the last 12 months (n = 160) and no NSSI episode in the previous 12 months (n = 160). Hayes’ PROCESS macro for mediation analysis in SPSS was used to test the hypothesized model.Results Participants with NSSI engagement in the last 12 months manifested significantly higher levels of depressive symptoms and loneliness. Conversely, young adults without NSSI engagement in the last 12 months manifested higher levels of social support from friends. This study found that social support from friends mediated the relationship between depressive symptoms and loneliness. Moreover, the moderation model was significant, explaining that the indirect effect of social support from friends was significantly stronger among participants without NSSI engagement in the last 12 months.Conclusions This study highlights the intricate interplay between depressive symptoms, loneliness, and social support from friends in a sample of Portuguese young adults with NSSI engagement behaviors in the last 12 months. These findings emphasize the need for a better understanding of factors that contribute to NSSI engagement behaviors particularly among young adults.