We aimed to examine the effects of a 16-week multimodal exercise program (MEP) on activities of daily living (ADL) in individuals with dementia (IWD). Furthermore, we investigated the participants’ individual response to the MEP and whether baseline cognitive and motor performance explain ADL performance. We conducted a multicenter randomized controlled trial (RCT) involving 319 participants aged ≥ 65 years with mild to moderate dementia. ADL were assessed at baseline and after the 16-week intervention using the Barthel Index (BI), the Erlangen Test of Activities of Daily Living (E-ADL) and the 7‑item Physical Performance Test (PPT-7). We additionally assessed cognitive and motor performance using standardized and validated assessments. Intervention effects were examined through two-factor analysis of variance with repeated measurements applying a per protocol and an intention-to-treat analysis. We compared baseline cognitive and motor performance between positive-responders (positive-R), non-responders (non-R), and negative-responders (negative-R) and examined cognitive and motor performance as potential cofounders of ADL by conducting multiple regression analyses. ... mehrThere were no significant time×group effects on ADL. Between 20 and 32% of participants responded positively to the intervention, i.e., improved ADL performance from baseline to follow-up. Positive-R had worse baseline motor performance compared to non-R. Cognitive and motor performance explained up to 51.4% of variance in ADL. The MEP had no significant overall effect on ADL in IWD. This may be related to insufficient exercise intensity. However, our results indicate that the response to the MEP depends on individual prerequisites which should thus be considered in further research on individual exercise approaches.