In the context of Iranian higher education, where self-regulation is crucial for students’ academic success amid evolving pedagogical approaches, this study examined the comparative effectiveness of two learner-centered instructional models—self-determination–based instruction (SDI) and flipped instruction—in enhancing university students’ self-regulation. Participants included forty-five undergraduate psychology students from Islamic Azad University, Eslamshahr, who were assigned to two experimental groups and one control group. Each group received 10 structured instructional sessions, and students’ self-regulation was assessed at pretest, posttest, and follow-up using the Motivated Strategies for Learning Questionnaire (MSLQ). For data analysis, separate analyses of covariance (ANCOVA) were conducted for posttest and follow-up scores, with pretest scores entered as covariates to control for baseline differences among groups. Bonferroni-adjusted pairwise comparisons were performed to examine group differences. Results indicated that both instructional interventions significantly improved students’ self-regulation compared with traditional instruction, with a large effect size (partial η² ranging from .36 to .41). The SDI group demonstrated the greatest gains and significantly outperformed the flipped instruction group. Effects remained stable from posttest to follow-up, indicating the durability of the intervention outcomes. By emphasizing autonomy, competence, and relatedness in instructional design, these findings highlight the theoretical and practical significance of self-determination principles in fostering enduring self-regulation skills in higher education, providing evidence-based guidance for curriculum developers and university instructors to enhance students’ independent and self-directed learning capacities.