The role of existential/spiritual domain of personality in adolescent health behavior is an underinvestigated research field in health psychology. The present study is based on the results of a research carried out in a sample of Transylvanian adolescents (N = 406; aged between 15–18 years, mean age = 16.5 year; 42.1% males and 57.9% females) focused on the association between meaning of life and health and risk behaviors. Calculating odds ratios, our analyses revealed an inverse direction in their relationships with searching for meaning of life and hopelessness (for example, for the relationship between searching for meaning and risk behavior: OR = 0.798, 95% CI = 0.674–0.946, p < 0.01; whereas for the relationship with hopelessness: OR = 1.149, 95% CI = 1.032–1.279, p < 0.05). These data point out that searching for meaning in life is not a negative status or a deficiency but on the contrary, it is more a cognitive-motivational structure that is linked to determining meaning. On the other hand, the results highlight that in adolescence the influence of searching for meaning is more determinant in terms of health and risk behaviors than meaning of life itself.