Background <p>Suicide is a critical and complex global public health issue. Understanding its less-studied underlying personality structure may be insightful for improved risk assessment and prevention. This study assessed the temperament and character profiles of suicide attempters using Cloninger’s psychobiological model.</p> Methods <p>A case–control study was conducted with 111 suicide attempters by poisoning and 99 matched controls in southern Iran between March 2021 and December 2021. Personality disorders and traits were assessed using the Temperament and Character Inventory (TCI).</p> Results <p>A significant overall difference was observed in TCI profiles between groups (<i>F</i> = 11.7, <i>P</i> &lt; 0.001). Post hoc analysis of TCI domains showed that, compared to controls, suicide attempters had significantly higher novelty seeking (<i>P</i> &lt; 0.001) and significantly lower cooperativeness (<i>P</i> &lt; 0.001) and self-directedness (<i>P</i> &lt; 0.001). The prevalence of personality disorders was over three times higher in attempters than in controls (55.9% vs. 18.2%; <i>χ</i>² = 31.5, <i>P</i> &lt; 0.001). Among attempters with a personality disorder, cluster B types were most prevalent (58.06%). About personality traits, analysis showed that narcissistic, histrionic, and obsessive–compulsive traits were most frequent among attempters, while controls were more likely to have avoidant traits or no prominent traits, i.e., indistinguishable (32.32% vs. 8.11%; <i>χ</i>² = 47.3, <i>P</i> &lt; 0.001).</p> Conclusions <p>This study found a distinct personality profile, marked by high novelty seeking and low self-directedness and cooperativeness, which was associated with a suicide attempt. This profile correlated with a higher rate of personality disorders, particularly within cluster B. Assessing such specific TCI dimensions might implicate clinical suicide risk evaluation.</p>