The psychological flexibility model (PFM) provides a framework for understanding and treating behavioural dysregulation in addictions. Rather than modulating the intensity of subjective experience, interventions based on, or consistent with, the PFM (PFM interventions) seek to alter the individual’s relationship to internal states, such as craving, negative affect and drug-related thoughts, using mindfulness, acceptance and related strategies. Experimental (non-clinical) studies in smokers have examined the effects of specific isolated strategies informed by or consistent with the PFM (PFM strategies). Here, we systematically review these studies and determine the extent to which they conform to methodological standards indicative of high levels of internal validity. Eligible studies were identified through electronic database searches and assessed for the presence of specific methodological features. Provisional aggregate effect sizes were determined depending on availability of data. Of 1499 screened publications, 12 met the criteria. All examined aspects of private subjective experience relevant to abstinence (craving n = 12; negative affect n = 10), demonstrating effects favouring PFM strategies relative to inactive control conditions. However, only six assessed outcome domains consistent with the PFM and provided no consistent evidence favouring PFM strategies. Overall, most studies had methodological limitations. As such, high-quality experimental studies continue to be needed to improve our understanding of necessary and/or sufficient constituents of PFM-guided smoking cessation interventions. Recommendations for future research are discussed