Abstract Background The use of social media by adolescents has increased considerably in the past decade. With this increase in social media use in our daily lives, there has been a rapidly expanding awareness of the potential unhealthy lifestyle-related health effects arising from excessive, maladaptive, or addictive social media use. Objective This study aims to assess the association between adolescents’ social media use and health-related behaviors. Methods We used a cross-sectional research approach and analyzed data from 96,919 adolescents at high schools throughout the Netherlands. A structured 43-item questionnaire was used to gather data on sociodemographics, dietary and lifestyle factors, and the degree of social media use based on the Compulsive Internet Use Scale. Logistic regression analyses were performed to assess the association between problematic social media use (PSMU) and lifestyle behaviors while adjusting for sociodemographic factors. Results Of the 96,919 included adolescents, 7.4% (n=7022) were identified as at risk for PSMU. Furthermore, logistic regression results showed that adolescents who are at risk for PSMU were more likely to report alcohol consumption and smoking while simultaneously having significantly lower levels of health-promoting behavior such as healthy eating habits (eating fruits, vegetables, and breakfast regularly) and physical activity. Conclusions This study confirms that adolescents at risk of PSMU were more likely to exhibit an unhealthy lifestyle. Being at risk for PSMU was a determinant of soft drug use, alcohol consumption, smoking, poor eating habits, and lower physical activity independent of the additional adjusted covariates including demographic variables and remaining lifestyle variables. Future research is needed to confirm this observation in an experimental setting.