This systematic review aims to summarize and update the current knowledge on the effectiveness of the existing interventions for alleviating loneliness and social isolation among older persons. A search of PubMed, ISI Web of science, SCOPUS, The Cochrane Library, and CINAHL databases was performed. The terminology combined all possible alternatives of the following keywords: social isolation, loneliness, old people, intervention and effectiveness. Eligible studies were published between January 2011 and February 2016 in English or Italian language and regarded the implementation of loneliness/social isolation interventions among the older generations. Outcome measures in terms of the intervention effects needed to be reported. In total, 15 quantitative and five qualitative studies were ultimately included in this review. Eighteen interventions were reported across the quantitative studies. Six out of 11 group interventions (55%), one out of four mixed interventions (25%) and all three individual interventions reported at least one significant finding related to loneliness or social isolation. Our review suggested that new technologies and community engaged arts might be seen as a promising tool for tackling social isolation and loneliness among the older individuals. Future studies need to work on methodological quality and take into consideration the suggestions of the present literature in order to provide firm evidence.