Background: Smoking and smoking-related disease is endemic amongst many marginalised populations such as people experiencing homelessness, people who use drugs, people living with HIV, sex workers and members of the LGBTQ+, Indigenous, Traveller and migrant communities. Alternative Nicotine Delivery Systems (ANDS)-based interventions including those using Nicotine Replacement Therapy (NRT) and Electronic Nicotine Delivery Systems (ENDS) show promise in supporting people to reduce their smoking. However, little is known about ANDS-based smoking reduction interventions with marginalised populations. This systematic review provides a best evidence synthesis of ANDS-based smoking reduction interventions to address this gap.Methods:A systematic review protocol was registered on PROSPERO (CRD42020158832) and literature review conducted through MEDLINE/PubMed, CINAHL, EMBASE, OVID SP, ScienceDirect and Google Scholar. The primary outcomes of cigarette smoking, and biochemical validation of abstinence were reported. Secondary outcomes reported included physical health, mental health and other outcomes.Results: Twenty-Nine studies were included in this review. Thirteen of the included studies were randomised controlled trials (RCTs) (n= 2828) and 16 studies were quasi controlled studies (n=1172). The sample size across the studies ranged from 9 to 775 participants. The mean reported age of participants ranged from 32.4 to 56.9 years old with an overall mean age of 39.55. A minority of study participants identified as female (33.43%; with two studies not reporting gender). A range of ANDS-interventions were found to be effective in reducing smoking amongst a range of marginalised groups. However, the overall quality of both the controlled and quasi experimental studies, as evaluated using the JBI Appraisal Tool, was found to be low.Conclusions: Studies are often evaluated as homogenous interventions although they are frequently a group of interventions and lack power analysis of the effects of individual components of the intervention effect. Several studies suggest potential mental health benefits consequent of ANDS-based intervention, though this effect is poorly explored. There is a current lack of RCTs related to ANDS-based smoking related interventions with people experiencing homelessness. Similarly, there is a lack of properly controlled RCTs exploring the use of ENDS with marginalised populations. Future studies should aim to address these deficits.