Although home-dwelling older adults are frequently assisted with polypharmacy management by their informal caregivers, they can still face medication-related problems. Identifying older adults’ and their informal caregivers’ beliefs about medication is a gateway to understanding and improving medication adherence. This study aimed to analyse beliefs about polypharmacy among home-dwelling older adults with multiple chronic conditions and their informal caregivers, focusing on their daily medication practices. Semi-structured interviews were conducted with 28 older adults, 17 informal caregivers, but also 13 healthcare professionals. Based on an inductive methodological approach, data were analysed using thematic content analysis. Interviews revealed the different attitudes adopted by older adults and their informal caregivers in relation to the treatment information provided by healthcare professionals. A variety of beliefs were identified and linked to medication adherence by examining daily medication practices. Polypharmacy was experienced as a habit but also an obligation, highlighting some of the strategies and negotiations underlying medication use at home. Collecting viewpoints from multiple stakeholders is an innovative way of accessing and analysing beliefs about polypharmacy. Daily medication practices provided information about medication beliefs and may contribute to developing targeted professional interventions that improve medication adherence.