Chewing-side preference (CSP) may be associated with dominant cerebral hemispheric organisation. However, little information exists regarding whether CSP is reflected by preferential activity in the opposite (to the CSP) cerebral hemisphere. The aim of this study was to investigate the effects of CSP on cerebral cortex response to bilateral tooth clenching. Sixteen right-handed participants with left (two men: 29·0±8·4 years old, six women: 32·3±4·8 years old) or right (four men: 31·0±6·1 years old, four women: 30·8±4·7 years old) CSP were scanned by functional magnetic resonance imaging during moderate levels of voluntary tooth clenching. The on-off sequence of scanning was 30 s of clenching (on) and 30 s of rest (off) a total of five times. The results showed that blood oxygen level-dependent signals in the contralateral (to the CSP) primary sensorimotor cortex increased more than in the ipsilateral primary sensorimotor cortex in participants with both left and right CSP (P≤0·001). The supplementary motor area was activated in participants with left (P≤0·001) but not right CSP. Activation of the inferior frontal gyrus and inferior parietal lobule was greater in participants with right versus left CSP (P≤0·001). Significant (P≤0·001) activation was observed in the parahippocampal gyrus in five of eight participants with left CSP, whereas no activation was observed in those with right CSP. These findings suggest a relationship between hemispheric dominance and CSP in the primary sensorimotor cortex responsible for bilateral tooth clenching.