Children and adolescents consume sugar-sweetened beverages (SSBs) excessively, which is associated with childhood obesity, dental caries, and increased risk for cardiovascular disease and type 2 diabetes. Interventions spanning the socio-ecological model (i.e., intrapersonal, interpersonal, environmental, policy) have been shown to reduce SSB consumption under controlled conditions. However, not much is known about their potential to work under "real-world" conditions. This information can ensure that effective programs reach populations that could most benefit, such as children and adolescents in Central Appalachia, who consume three to four times more SSBs than their American peers. Central Appalachia is a rural, geographically isolated region where attempts to reduce SSBs are challenged by limited resources, skepticism toward health programs/providers, and pervasive cultural norms around SSBs. This dissertation describes three studies (2014-2016) that address these challenges by testing multi-level interventions that prioritize cultural acceptability and feasibility. The first study was a systematic review of child and adolescent SSB studies using the RE-AIM (reach, efficacy/effectiveness, adoption, implementation, maintenance) framework to evaluate whether studies reported elements necessary for replicability, such as resources needed for delivery or factors that might prevent participation. The review revealed that available evidence does not provide this information, and recommended that future studies prioritize evaluating and reporting these elements. The second and third studies describe methods to test implementation of Kids SIPsmartER, a theory-based program targeting various socio-ecological levels, in an Appalachian Virginia county. The second study engaged a group on local middle school youth (n=9) in adapting the program, which targeted universal theoretical constructs, to ensure that it was culturally acceptable and demonstrated potential to generate community-wide changes. The third study used a randomized controlled design to determine whether Kids SIPsmartER was feasible as a school-based program. This study tested the program's potential reduce SSBs, as well as whether it was accepted, in demand, and able to be practically implemented within schools, the most common gathering place for rural adolescents. Taken together, these studies provide the foundation for larger, more controlled studies that prioritize both efficacy and replicability, in order to reduce the disproportionate burden of SSBs and associated diseases across Central Appalachia.