Introduction Irrational medicine use is proportionately higher in low and middle-income countries like Sierra Leone. This study aims at exploring the structure, functions, and challenges of Drug, and Therapeutics Committees (DTC) recently piloted in Sierra Leone. Method A two-phase mixed-method study design was used in this study. Firstly, a cross-sectional survey using an online questionnaire to assess the structure, indicators, and challenges of DTC . In phase two, a semi-structured interview was used to get deeper insights into the key issues that emerged from the survey. Participants were mainly pharmacists in-charge at the hospitals where the DTC program hasbeen established. MS Excel 2019 and NVivo version 12 were respectively used for data management and analysis. Results DTCs mostly had a minimum of ten members consisting of a mix of both medical and hospital administrative staff. The main functions of DTC are ensuring rational medicines use, monitoring, and reporting adverse drug reactions. All but one hospital had subcommittees that are either effective or nonfunctional. The main challenges in DTC functions and maintenance were funding (n=6), DTC decision implementation (n=4), and unmotivated members (n=4). Strategies suggested to improve DTC at public hospitals and nationwide include; resource allocation, monitoring, and evaluating DTC functions and capacity building of its members. Conclusion DTC present a compelling opportunity towards achieving rational medicines use at the hospital level in Sierra Leone. Nonetheless, lack of funding, operational resources, are significant limitations. Policymakers must note these drawbacks whilst expanding DTC programs to other hospitals in Sierra Leone.