In a minority of cases, problematic use of technology can negatively impact on adolescents and impair some aspects of their social, emotional, and psychological development. The purpose of the present study was to examine the direct and indirect effects of problematic Instagram use (PIU) on different psychopathological outcomes including loneliness, depression, anxiety, and social anxiety via body image dissatisfaction (BID). Additionally, moderating role of gender on the relationships among variables was investigated. A total of 491 adolescents (M-age = 15.92 years, SDage = 1.07; range = 14 to 19 years) were recruited for the study to complete a questionnaire that included the relevant assessment tools for the aforementioned variables. Mediation and moderation analyses showed that among male adolescents, PIU was directly associated with loneliness, depression, general anxiety, and social anxiety and BID partially mediated these associations. Among females, PIU was directly associated with depression and indirectly with general anxiety and social anxiety via BID. Gender significantly moderated the direct relationships of PIU with loneliness, general anxiety, and social anxiety. PIU was directly associated with loneliness, general anxiety, and social anxiety among males only, whereas among females, PIU was indirectly associated with general and social anxiety via BID but was not related to loneliness. Results of this study indicate that PIU has different negative psychological effects on male and female adolescents and that BID appears to be one explanatory factor for these impairments especially among females.