The last few years have seen the emergence of new psychoactive substance among the homeless population, specifically synthetic cannabinoid receptor agonists. The purpose of this study is to investigate the knowledge and experiences of new psychoactive substances amongst users from the homeless population. An explanatory research design was applied using a semi-structured questionnaire with the focus on gaining insights on the prevalence, motivations and effects. Participants were recruited through convenience sampling from support organisations and charities UK-wide. Descriptive statistics and logistic regression were applied to analyse the data obtained from participant surveys. A total of 105 participants met the inclusion criteria and were in the age range of 18 to 64 years old. Almost 70% consumed new psychoactive substance products, which “Spice” was the most prevalent substance. Homeless users had consumed new psychoactive substance to escape reality and to self-treat themselves and stopped consumption due to the adverse effects. Adverse events were reported from the majority of the participants and led to more than 20% of the participants requiring medical treatment following hospitalisation. Findings from this study can contribute to the development of guidelines and policies that specifically address the needs of the homeless population who use new psychoactive substances.