Background: Deprescribing is of particular importance in older adults with limited life expectancy since this population group is highly susceptible to the potential harms of inappropriate medications. Objective: This systematic review aimed to explore attitudes towards deprescribing among older adults with limited life expectancy and their relatives. Methods: A systematic literature review was conducted in the MEDLINE and EMBASE databases from inception to October 2019. Inclusion criteria were studies specifically describing attitudes towards deprescribing among older adults (≥ 65 years) with limited life expectancy and/or their relatives regardless of study type. Results were analyzed, inspired by the Joanna Briggs Institute’s method for synthesis of qualitative data. Results: A total of 842 studies were identified and screened; 84 were full-text assessed for eligibility and 7 were ultimately included. Two studies investigated the attitudes of older adults with limited life expectancy and their relatives towards deprescribing of statins and donepezil, respectively, while the five remaining studies related to attitudes towards deprescribing in general. Four main themes were identified: (1) the well-being of older adults with limited life expectancy; (2) involvement of older adults and their relatives in deprescribing; (3) the role of health care professionals in deprescribing; and (4) medication-related factors affecting deprescribing. Within each of these themes, several subthemes were identified. Conclusions: Attitudes towards deprescribing among older adults with limited life expectancy and their relatives vary and highlight several barriers and enablers to the deprescribing process. Several of these factors must be addressed to successfully implement deprescribing initiatives in this patient group.