The purpose of this study was to investigate the influence of students' motivational beliefs (learning goal orientation, task value and self-efficacy) in science learning on students' self-regulation in the science classroom. The study also examines the moderating effect of gender on the proposed relationships. Data were collected from 719 boys and 641 girls across grades 8, 9 and 10 in 5 public schools in Perth, Western Australia. Results from structural equation modeling analysis indicated that all 3 motivational constructs were strong predictors of students' self-regulation in science learning. The multi-group analysis to examine gender differences revealed that the influence of task value on self-regulation was statistically significant for boys only. The findings present possible opportunities for educators to plan, and to put into practice, effective intervention strategies aimed at increasing students' self-regulation in science learning. The core feature would be to target and develop students' motivational beliefs of learning goal orientation and self-efficacy in science learning. Additionally, for boys, the intervention strategies would be to elevate boys' perspectives of science task value.