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Abstract Background Truck drivers are a vital workforce, but have higher rates of obesity and other chronic diseases than the general population. The occupation’s sedentary nature, limited physical activity opportunities and access to healthy food, and irregular sleeping patterns contribute to poor health. This systematic review and meta-analysis aimed to evaluate the effectiveness of interventions on health behaviours and cardiometabolic biomarkers of health in truck drivers. Methods A systematic search was conducted in February 2024, and reported according to PRISMA 2020 guidelines. Experimental studies targeting physical activity, sedentary behaviour, sleep, diet, weight loss, drug/alcohol use, and/or smoking were eligible. Two reviewers independently screened and completed data extraction and risk of bias assessment. Data were combined at the study level. Pooled statistics were calculated using mean differences (MD) or standardised mean differences (SMD) for outcomes that were reported in ≥2 studies. Pre- and post-intervention means and standard deviations (SD) for the intervention and control groups were used to compute effect sizes. Results Nineteen studies (n=2137 participants) were included. Meta-analyses found a small-to-moderate increase in fruit and vegetable consumption (SMD 0.32, p=0.03) with no other significant effects on other outcome variables. Conclusions Interventions are moderately effective in increasing truck drivers’ fruit and vegetable consumption, but not other outcomes. There is a dearth of research in the driver population compared to other occupational groups. Future interventions should consider workplace and environmental factors to promote the health and wellbeing of truck drivers. Trial registration The study protocol was registered on PROSPERO (CRD42021283423).