Service providers in rural communities are experiencing increasing demand to provide interventions to address loneliness and social isolation without clear evidence of what is effective. This mixed-methods review aimed to synthesize the evidence to establish the effectiveness of loneliness and/or social isolation interventions in rural adult populations worldwide, published in English before September 2020. Eighteen papers were retrieved, including eight quantitative papers, six qualitative papers, and four mixed-methods papers. Following a segregated convergent design, four analytical themes emerged through thematic analysis: connecting to the cyber world, social connections, companionship, and volunteering. The integration of the qualitative and quantitative results is presented under each analytical theme. The limited research suggests interventions that focus on shared interests and common experiences can decrease feelings of loneliness, but there is limited evidence of the effect on reducing social isolation. There is a need for more well-conducted studies of the effectiveness of interventions for preventing and reducing loneliness and social isolation interventions in rural populations.