The present study explores gender differences in adolescence with regard to meaning in life and self-control skills and in relation to positive and negative affect. Participants were 500 adolescents between the ages of 13 and 16 years. Outcomes revealed that females reported higher negative affect and self-control skills in comparison with males. Moreover, the association between self-control skills and negative affect was stronger among females than among males. In contrast to our assumptions, positive affect was not found to be higher among females although females scored higher in meaning in life than their male counterparts. In addition, self-control skills mediated the association between meaning in life and negative affect, and gender moderated the association between self-control skills and negative affect only among females. Considering these findings, gender seems to be vital in explaining differences in the use of self-control skills and meaning in life and their links to positive and negative affect.