Background <p>Medical students encounter sustained academic, evaluative, and emotional demands that are relevant not only to psychological symptoms but also to positive psychological functioning. The present study focused on psychological well-being to capture eudaimonic dimensions of functioning, including self-acceptance, autonomy, purpose in life, and personal growth. Guided by multidimensional perfectionism theory, self-conscious emotion theory, and cognitive-regulatory accounts of rigidity and flexibility, this cross-sectional study examined the indirect associations of self-oriented perfectionism with psychological well-being through perceived cognitive flexibility and shame among Iranian medical students.</p> Methods <p>This cross-sectional study was conducted among medical students at Shahid Beheshti University of Medical Sciences from November 21, 2024, to July 21, 2025. Data were collected online using the Porsline platform. After excluding incomplete responses and outliers, 801 participants were retained for the primary analysis. Measures included the self-oriented perfectionism subscale of the Multidimensional Perfectionism Scale, the shame subscale of the Guilt and Shame Proneness Scale, the Cognitive Flexibility Inventory, and the short form of Ryff’s Psychological Well-Being Scale. Data were analyzed using IBM SPSS Statistics 27 and Hayes’ PROCESS macro (Model 4). Pearson correlations and parallel indirect-effects models were estimated using 5,000 bias-corrected bootstrap resamples with 95% confidence intervals and HC4 heteroskedasticity-consistent standard errors.</p> Results <p>Self-oriented perfectionism was inversely associated with perceived cognitive flexibility and psychological well-being, and positively associated with shame. In the primary model, the total indirect estimate was significant, B = − 0.135, 95% CI [− 0.175, − 0.096], with significant specific indirect estimates through perceived cognitive flexibility, B = − 0.119, 95% CI [− 0.158, − 0.085], and shame, B = − 0.016, 95% CI [− 0.031, − 0.003]. After controlling for age and gender, the total indirect estimate remained significant, B = − 0.131, 95% CI [− 0.173, − 0.094], as did the indirect estimates through perceived cognitive flexibility, B = − 0.110, 95% CI [− 0.148, − 0.074], and shame, B = − 0.021, 95% CI [− 0.037, − 0.007]. The adjusted model accounted for 47.4% of the variance in psychological well-being.</p> Conclusions <p>Self-oriented perfectionism was associated with lower psychological well-being among medical students, with statistically significant indirect components through lower perceived cognitive flexibility and higher shame. The indirect association through perceived cognitive flexibility was larger, whereas the shame pathway was statistically significant but comparatively small. Given the cross-sectional and self-report design, these findings should be interpreted as associations rather than evidence of temporal ordering or causal mechanisms.</p>