Abstract Background The use of Complementary and alternative medicine (CAM) in chronic liver disease (CLD) patients in Germany is unknown. This study investigated the frequency of CAM use and associated sociodemographic, clinical and personality factors in CLD patients in Germany. Methods This is a cross-sectional multicenter study of CLD patients attending liver outpatient clinics of university hospitals in Halle(-Saale) and Homburg between 2015 and 2017. Dedicated questionnaires recorded CAM use, sociodemographic and personality factors (evaluated with the “Big five” model, “Hospital Anxiety and Depression”-, “Multidimensional Health Locus of Control”- score). Uni- and multivariate analyses assessed factors associated to CAM use. Results Overall 378 patients were recruited, 92 (24.3%) reported to CAM use. On univariate analysis, female CAM users were older (p = 0.001) and more physically active (p = 0.002), male CAM users more often used homeopathy (p = 0.000), actively promoted their health (p = 0.010) or had UDC in their medication (p = 0.004). Logistic regression analysis adjusted for personality factors showed significant association of age, physical exercise (females) and satisfaction with alternative medicine (females, males) to CAM use. Conclusions CAM use is prevalent among CLD patients in Germany and is significantly associated to satisfaction with alternative medicine (females, males), physical exercise and older age (females). Doctors should actively inquire CLD patients about CAM use, as hepatotoxicity or interaction with medication can occur.