Internationally, health systems face an increasing demand for services from people living with multimorbidity. Multimorbidity is often associated with high levels of treatment burden. Targeting lifestyle factors that impact across multiple conditions may promote quality of life and better health outcomes for people with multimorbidity. Motivational interviewing (MI) has been studied as one approach to supporting lifestyle behaviour change. A systematic review was conducted to assess the effectiveness of MI in healthcare settings and to consider its relevance for multimorbidity. Twelve meta-analyses pertinent to multimorbidity lifestyle factors were identified. As an intervention, MI has been found to have a small-to-medium statistically significant effect across a wide variety of single diseases and for a range of behavioural outcomes. This review highlights the need for specific research into the application of MI to determine if the benefits of MI seen with single diseases are also present in the context of multimorbidity.