Insights in the challenges that healthcare providers encounter in serving low health literate patients is lagging behind. This study explored challenges perceived by healthcare providers and provides strategies in communication with low health literate patients. Primary and secondary healthcare providers (N = 396) filled in an online survey. We assessed the frequency of challenges prior to, during and following a consultation, and which strategies were used and recommended. Survey outcomes were validated in in-depth interviews with healthcare providers (N = 7). Providers (76%) reported one or more challenges that were subscribed to patients’ difficulties in comprehending or applying health-related information, in communicating with professionals, or in taking responsibility for their health. Providers (31%) perceived difficulties in recognizing low health literate patients, and 50% rarely used health literacy specific materials. Providers expressed needs for support to recognize and discuss low health literacy, to adapt communication and to assess patient’s comprehension. Future research should focus on developing strategies for providers to ensure patients’ understanding (e.g. applying teach-back method), to recognize low health literate patients, and to support patients’ in taking responsibility for their health (e.g. motivational interviewing)