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Background The study explores the language barriers between two language minority populations and healthcare professionals in the Volta Region of Ghana. Methods An interpretive description with a qualitative approach to data collection and analysis was used. This study was carried out in the Tafi-Atome and Avatime-Vane communities, the Hohoe Municipal Hospital and the Margaret Marquart Catholic Hospital in the Kpando Municipality. In all, 46 respondents comprising 19 purposively sampled community members (patients) from the two selected communities and 27 conveniently sampled healthcare professionals from the two health facilities were interviewed. The face-to-face in-depth interviews were audio-recorded, transcribed and thematically analysed. Results The study revealed a barrier in language use between healthcare professionals and patients from the two language minority communities. While healthcare professionals preferred to use English, Akan and Ewe, the patients, on the other hand, preferred their native languages, which are Sideme and Tegbor. The services of unqualified interpreters were utilised by both healthcare professionals and patients. Study participants were aware of these challenges, which prevented the patients from receiving optimum healthcare services, and the healthcare workers from delivering client-centred healthcare services. Conclusions The presence of communication challenges emanating from language barriers between healthcare professionals and patients should be considered as a key hindrance to the attainment of the Sustainable Development Goal Three (SDG3), which aims to promote health and well-being at all ages. Therefore, stakeholders in the healthcare delivery system in Ghana need to prioritize stronger communication and translation practices and policies.