Introduction: This study aimed to investigate the relationships between neurological soft signs (NSS), circadian preferences, and emotional regulation difficulties in patients with bipolar disorder (BD) and their unaffected first-degree relatives (FDRs). Materials and Methods: A total of 105 people (35 BD patients, 35 FDRs, and 35 healthy controls) enrolled in the study. They completed a sociodemographic information form, the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Morningness-Eveningness Questionnaire (MEQ), Difficulties in Emotion Regulation Scale (DERS), and Neurological Evaluation Scale (NES). Results: NES motor coordination, complex motor movements, other subscale and total scores we re significantly higher in BD and FDRs compared to the control group. The subscales of the DERS including nonacceptance, goals, impulse, strategies, accessibility, and total DERS scores were also significantly higher in patients than the relative and control groups. A statistically positive, weak, and significant relationship emerged between the patient group’s ot her NES sub-dime nsion and the DERS sub-dimensions of impuls e and awareness. Meanwhile, significant relationship was found in the FDRs between NSS and the NES sub-dimensions emotional integration and complex motor movements. A significant relationship was also found between the DERS sub- dimension nonacceptance and the NSS sub-dimension complex motor movements. Conclusion: This study discovered that NSS are associated with negative emotional regulation strategies in patients with BD during in euthymic period and FDRs. NSS and circadian preferences may be endophenotype candidates for BD.