INTRODUCTION: Sickle Cell Disease (SCD) is the leading genetic disease in sub-Saharan Africa and therefore remains a global public health threat. Use of complementary and alternative medicines (CAM) most especially herbal medicine (HM) in chronic diseases such as sickle cell disease has widely been reported in Africa where advanced technologies are greatly lacking. Despite a large presence of the sickle cell disease in Uganda, the extent to which herbal medicines are used in management of children with sickle cell disease has not been documented. This study purposed to determine the prevalence of herbal medicine (HM) use and associated factors among caregivers of children with SCD at Mulago National Referral Hospital. METHODS: a total of 384 child caretakers were interviewed in a descriptive cross-sectional quantitative study conducted at the Mulago Sickle cell clinic in March 2019. Enrolment was done consecutively and a structured interviewer administered questionnaire administered to collect data from the caretakers which was managed using SPSS version 23. Multivariate logistic regression was used to identify the factors associated with herbal medicine (HM) use. Factors with p-value <0.05 were regarded significant. RESULTS: the rate of herbal use was 77.6% (298 of 384 caregivers). At multivariate analysis, the odds of a caregiver who agreed that; HM cures symptoms faster than conventional medicine (CM) were 3 times those who disagreed with this statement (AOR =3.439, 95% CI: 1.447 - 8.176). The odds that a caregiver who agreed that HM has fewer side effects than CM were almost 4 times those that disagreed with this statement (AOR = 3.528, 95% CI: 1.917 -6.494). The odds that a caregiver who agreed that marketing HM through televisions adverts encourages HM use were 4 times those who disagreed with this statement (AOR = 4.185, 95% CI: 2.036 -8.603). CONCLUSION: this study reports a high prevalence of HM use among caregivers of children with SCD at Mulago Hospital, in Uganda. The practice is significantly influenced by caretakers´ perception that HM cures symptoms faster than CM, has fewer side effects and that telemarketing has greatly facilitated its use over CM. More effort is therefore needed to encourage clinic attendances and CM use and limit the unfounded TV adverts on HM. There is also need for studies to identify the common HM used so that their efficacy and safety are well studied.