Background: The amputation of a foot or a leg is one of the complications caused by diabetes that creates fear. After the amputation, the patient becomes dependent on a caregiver, who is often not prepared for this new phase of life. Knowing the factors that influence care delivery in caregivers of amputee type 2 diabetes patients is important from an heuristic point of view, since very few studies have focused on this population. Objectives: This study analysed the predictors and moderators of quality of life, in caregivers of amputee patients due to type 2 diabetes. Methods: This study has a cross‐sectional design. All ethical standards were followed in the conduct of this study. The sample comprised 101 caregivers who answered the following instruments: Carer's Assessment of Managing Index, Burden Assessment Scale, Depression Anxiety Stress Scales, Revised Impact of Events Scale, Family Assessment Device, Family Disruption from Illness Scale and the Short Form Health Survey‐36. Results: The practice of physical activity, lower burden, better family functioning and less traumatic symptoms were predictors of better mental quality of life. Having no chronic disease and less physical symptoms predicted better physical quality of life. Duration of care moderated the relationship between traumatic symptoms and mental quality of life, but not with physical quality of life. Receiving help in caregiving moderated the relationship between traumatic symptoms and mental quality of life. The limitations of this study include the exclusive use of self‐report instruments and the fact that the caregivers who have participated in this study were those who accompanied the patient to the hospital. Conclusion: In order to promote physical quality of life, future intervention programmes should consider the presence of chronic disease in the caregiver and the duration of care, as well as the caregivers’ physical symptoms.