The purpose of this study is to investigate the association between psychosocial factors, protective factors, and its associated triggers with psychological distress among Bolivian adolescents. This cross-sectional study was conducted by investigating the 2018 Bolivia global school-based student health survey (GSHS). The total number of students who participated in this survey was 7931, and the final sample was 7377. The mean age of the participants was 15.3 years (SD = 1.4). Psychological distress was assessed with a 2-item screener (loneliness and worry induced sleep disturbance). In all 22.3% of participants reported experiencing psychological distress, with 18.1% among adolescent males and 26.2% among adolescent females. In adjusted logistic regression analysis (AOR, 95% CI), there are two significant directions of association. One is the negative association, such as parental involvement as a protective factor. School adolescents who had more parental involvement were less likely to experience psychological distress. Parents understand problems or worries (0.64, 0.54–0.75, p < .001) and parents disregard privacy (0.69, 0.58–0.82, p < .001). On the other hand, many psycho-social factors are significantly positively associated with psychological distress. School adolescents who experience more psychosocial factors are more likely to experience psychological distress. Physical assault in the previous year (1.83, 1.59–2.11, p < .001), being bullied at school (1.27, 1.07–1.52, p < .01), being bullied outside of school (1.36, 1.15–1.61, p < .001), and being cyberbullied (1.60, 1.37–1.88, p < .001), were all significantly associated with psychological distress. Healthy relationships in a family, and interventions to reduce violence and bullying, should be encouraged and promoted.