Systemic thinking skills are an increasingly important aspect of contemporary life for all students. Therefore, the first aim of the present study was to investigate the relationship between systemic thinking skills, epistemological beliefs, and mathematical beliefs in a sample of 120 secondary school students aged 16-18 years in Saudi Arabia. The second objective was to examine gender differences in these three variables. Participants answered scales measuring the Systemic Thinking Inventory (STI) and the Mathematical Beliefs Scale (MBS) created by the researcher. Additionally, participants answered the Epistemic Belief Inventory (EBI). Results showed a positive correlation between systemic thinking skills, epistemological beliefs, and mathematical beliefs. In addition, significant differences were found in favor of men on the systemic thinking skills on the holistic vision of the system and systemic synthesis skills subscales and females on the systemic analysis subscale. Significant differences were found in epistemological beliefs. A particular difference was innate knowledge and omniscient authority in favor of males, simple knowledge, certain knowledge, and rapid learning in favor of females. In addition, differences were found for mathematics teacher competence and self-efficacy beliefs in favor of males and the usefulness of learning mathematics, difficulty in mathematics, and enjoyment of mathematics in favor of females. The results are discussed in light of the relevant literature, and suggestions are made.