Free sex has a negative impact on the biopsychosocial condition of adolescents. Free sex poses a real danger to reproductive health, including the transmission of Sexually Transmitted Infections (STIs), out-of-wedlock pregnancy, which consequently increases the abortion rate, psychological pressure, and depression. This study aims to analyze the biopsychosocial and spiritual factors of sexual behaviors of adolescents in an Islamic boarding school. It was designed as an analytic survey with a cross-sectional time approach conducted in 2021 with a sample of 384 adolescents aged 16-19 years who were selected through random cluster sampling. The data were collected through questionnaires and analyzed by confirmatory factor analysis using structural equation modeling. The results showed that there was an influence of spiritual biopsychosocial factors, namely biological factors with puberty as the indicator (T > 1.96; R square 0.213), psychological factors with self-efficacy, self-esteem, and emotional intelligence as the indicators (T > 1.96; R square 0.242), social factors with parents' role, peers' role, schools' role, teachers' role, Islamic boarding school education system, and social media's role as the indicators (T > 1.96; R square 0.187), spiritual factors with spiritual intelligence and religiosity as the indicators (T > 1.96; R square 0.332), as well as sexual perception with cognitive and affective indicators (T > 1.96; R square 0.310). Spiritual factors were the most dominant factor influencing the premarital sexual behavior of Muslim adolescents. It indicated that religiosity and spiritual intelligence served as protective factors in the premarital sexual behavior of Muslim adolescents.