Purpose <p>Cognitive flexibility is associated with various psychological processes and outcomes. However, its relationship with suicidal thoughts and behaviors (STBs) remains inconclusive. Clarifying this relationship is vital, as cognitive flexibility—particularly set-shifting—may offer valuable insights into the cognitive mechanisms that could either heighten or reduce vulnerability to STBs. This systematic review and meta-analysis aimed to quantitatively assess this relationship.</p> Methods <p>We conducted a comprehensive search across four major databases (PubMed, PsycINFO, Web of Science, and Scopus) to identify studies measuring cognitive flexibility through validated self-report tools or experimental tasks in conjunction with STB assessments. A random-effects model was employed to analyze the data, with moderator analyses exploring potential sources of heterogeneity.</p> Results <p>The meta-analysis included 42 studies, comprising 5,946 participants. Results indicated a small but significant negative association between cognitive flexibility and STBs (<i>r</i> =&#xa0;−&#xa0;0.132, <i>k</i> = 116, 95% CI [−&#xa0;0.202; −&#xa0;0.062], <i>I</i>^<i>2</i>= 90.1%, Q(115) = 1157.75, <i>p</i>&#xa0;&lt;&#xa0;0.001). Subgroup analyses revealed no significant moderation effects by gender or age group, cognitive flexibility or STB measure type, whether the outcome was suicidal ideation or attempts, or clinical diagnoses.</p> Conclusions <p>These findings suggest that higher cognitive flexibility may act as a protective factor against STBs, possibly by promoting adaptive problem-solving and coping strategies, although the effect sizes remain small. We conclude that cognitive flexibility represents only a modest component in the etiology of STBs. Future research should focus on refining the measurement of cognitive flexibility in suicide risk assessments and incorporating these insights into intervention designs to evaluate its causal role.</p>