Alcohol use disorder (AUD) is a serious public health problem. Over 3.3 million people worldwide die each year due to alcohol-related causes, which is almost 5.3% of all deaths. This systematic review examines the effectiveness of injectable naltrexone treatment for people with AUD based on randomized clinical trial studies conducted between January 2004 and December 2019. Following PRISMA-P, this review searched PubMed, PsycINFO, CINAHL, Cochrane Library, and Web of Science for relevant studies. The inclusion criteria were AUD treatment, injectable naltrexone, and randomized clinical trials. Only articles written in English, involving human participants, and published in peer-reviewed journals were considered for this review. A total of 11 studies met the inclusion criteria. Ten out of the 11 studies assessed the impact of injectable naltrexone in a 3- to 6-month follow-up period, with one study having a year follow-up. This systematic review indicates that overall, injectable naltrexone therapy produced positive AUD treatment outcomes, including reduced mean time to first drinking day and/or heavy drinking day, decreased number of drinking and/or heavy drinking days, and increased abstinence, frequently at a statistically significant level in the larger studies. However, in all studies, less than half of the participants were completely abstinent after receiving injectable naltrexone. Injectable naltrexone treatment along with psychosocial therapy holds promise for addressing AUD.