Aims Salivary amylase gene (AMY1) copy number variations (CNVs) correlate directly with salivary amylase activity and serum amylase levels. Previously, individuals with high AMY1 CNVs exhibited low postprandial glucose levels and postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may play a role in lowering the risk of insulin resistance. Methods We verified the relationship between AMY1 CNVs and homeostatic model assessment–insulin resistance (HOMA‐IR) in a cohort of 1257 Korean men aged 20–65 years who visited two medical centres for regular health check‐ups, and in subgroups of current smokers and regular alcohol drinkers. Individuals with fasting plasma glucose levels > 10.0 mmol/l, HbA1c ≥ 64 mmol/mol (8.0%) or who used oral hypoglycaemic agents or insulin were excluded. Results AMY1 CNVs correlated negatively with HOMA‐IR even after adjusting for covariates (e.g. BMI, systolic blood pressure, triacylglycerol, alcohol consumption, smoking and physical activity). When the participants were divided according to current smoking and alcohol consumption habits, negative correlations between AMY1 CNVs and HOMA‐IR were more evident among non‐smokers and regular drinkers and were non‐significant among smokers and non‐regular drinkers. Conclusions Low AMY1 CNVs correlated with high insulin resistance in asymptomatic Korean men, and such a relationship presented differently according to the status of smoking and alcohol consumption. What's new? Our study is the first to show the direct relationship between AMY1 copy numbers and homeostatic model assessment–insulin resistance (HOMA‐IR) in healthy Korean men. The negative correlation was consistent and significant in the subgroup of non‐smokers and regular alcohol drinkers, but not significant in the subgroup of smokers and non‐regular drinkers. This provides an additional clue suggesting some kind of mechanism through which salivary amylase acts on insulin sensitivity, although its role has been somewhat underestimated so far.