Background There is limited evidence on potential health benefits of active travel, independently of leisure-time physical activity (PA), with metabolic syndrome (MetS) in Latin-America. Objective To investigate the relationship between active travel and metabolic syndrome (MetS) and its components in a national representative sample of Chilean adults. Methods Cross-sectional study of 2864 randomly selected adults' participants enrolled in the 2009–2010 Chilean National Health Survey (CNHS). Self-reported PA was obtained with the validated Global PA Questionnaire and classifying participants into insufficiently active (< 150 min/week) or active (≥ 150 min/week). MetS was diagnosed from the modified Adult Treatment Panel (ATP) III criteria with national-specific abdominal obesity cut points. Multilevel logistic regression analysis was applied to estimate associations of travel PA with MetS and its components at a regional level, adjusted for socio-demographic characteristics and other types of PA. Results 46.2% of the sample engaged in 150 min/week of active travel and the prevalence of MetS was 33.7%. Mets was significantly lower among active travel participants. Active travel was associated with lower odds of MetS (OR 0.72; 95%CI 0.61–0.86), triglycerides (OR 0.77; 95%CI 0.64–0.92) and abdominal obesity (OR 0.82; 95%CI 0.69–0.97) after controlling for socio-demographics and other types of PA. Conclusion Active travel was negatively associated with MetS, triglycerides and abdominal obesity. Efforts to increase regional active travel should be addressed as a measure to prevent and reduce the prevalence of MetS and disease burden in middle income countries.