Community-based interventions using artemisinin-derived suppositories may potentially reduce malaria-related childhood mortality. However, their sociocultural acceptability is unknown in Papua New Guinea and a formal examination of caregiver’s attitudes to rectal administration was needed to inform effective deployment strategies. Caregivers (n = 131) of children with uncomplicated malaria were questioned on their prior experience with, and attitudes to, rectal administration and then offered artesunate suppositories as treatment of their child. The 29% who refused this alternative were further questioned to determine their reasons for this refusal. Lack of spousal approval and fear of side effects were the most common reasons for refusal. Sixty-six percent of caregivers agreed to self-administer suppositories, which were perceived as effective (99%), safe (96%), and fast-acting (91%), but problematic to administer to a struggling child (56%). Shame, embarrassment, and hygiene were not significant concerns. Acceptability of rectal administration should be relatively high in Papua New Guinea. However, deployment must be accompanied by health education that addresses the practical aspects of administration, is appropriate for the illiterate, and is directed at fathers as well as mothers.