This study was designed to investigate the association of oral ulceration and oral health factors, together with psycho-social well-being in Behçet’s disease (BD), and to clarify the importance of psycho-social support of patients in the overall management of BD. The study comprised of a cohort of 146 BD patients (mean age ± SD = 39.65 ± 13.20) and 20 recurrent aphthous stomatitis (RAS) patients (mean age ± SD = 42.32 ± 11.32). Oral ulcer severity score (OUSS), Behçet’s disease current activities form (BDCAF), hospital anxiety and depression scale (HADS), and the work and social adjustment scale (WSAS) were investigated. Oral health risk factors were also included. The analysis of variance, regression, and factor analysis were used to scrutinise the data. Almost 73% of patients were at high caries risk in BD and RAS groups. Thirty-nine percent of BD and forty percent of RAS had a score of BPE3 (probing depth 3.5–5.5 mm). Regression analysis revealed that OUSS and WSAS had a positive impact to increase the BDCAF score in BD patients (β = 0.395, P = 0.001; β = 0.240, P = 0.019), respectively. Dental health, periodontal health, anxiety, depression, and WSAS variables had strong loadings by factor analysis based on gender and at the time of present and absent of oral ulceration. The main oral ulcer characteristics that had significant influences on the total of oral health quality of life by 68.6% were: size, duration, ulcer-free period, and pain. The results highlighted the significant influence of oral ulceration, patients’ oral health, diet, and psycho-social well-being as multi-factorial causes on increasing disease activity in BD patients.Electronic supplementary materialThe online version of this article (10.1007/s00296-018-4117-y) contains supplementary material, which is available to authorized users.