Background: Harmful substance use is a major challenge globally with far reaching detrimental effects on social, economic and health systems. This burden weighs more heavily on underdeveloped countries as they do not have the infrastructure needed to manage the consequences of substance use. In high-income countries, several evidence-based brief intervention models are used for HSU including Motivational Interviewing (MI). However, fewer studies have been conducted in low-resource settings. Aim: In this review, we systematically reviewed studies utilising motivational interviewing as a component of interventions with adults presenting with harmful substance use in LMICs. Methods: Adhering to Cochrane and PRISMA guidelines, we systematically searched for studies published between 2010 and 2022. The search was conducted in PubMed, EBSCOhost, Web of Science, the Cochrane Library, clinicaltrials.gov and the GSK Clinical Study Register. A narrative analysis was done, and The Joanna Briggs Institute (JBI) Critical Appraisal Tools were used to assess the quality of the studies included. Results: The search yielded 518 publications. Eleven studies from five different countries met inclusion criteria. These consisted mainly of RCTs with some employing qualitative or mixed methods approaches. The focus of the interventions varied, with most targeting alcohol use, while a few addressed opioids, and other drugs. The interventions used different strategies, including MI blended with other interventions (such as CBT, BA, and imaginal desensitization) or using MI-informed approaches. Overall, MI was shown to improve substance use outcomes in seven of the 11 studies with significant reduction in substance use based on outcomes measured. Conclusions: This review highlights that, interventions incorporating MI demonstrated positive effects in improving substance use outcomes in the majority of the studies reviewed. Further research with larger sample sizes and more rigorous study designs is necessary to strengthen the evidence base and address potential sources of bias.