OBJECTIVES: Although previous studies suggest that dietary texture-driven masticatory activity is correlated with stress tolerance, the underlying mechanisms, including neurotransmitter dynamics, remain unclear. This study investigated the effects of dietary texture-driven masticatory activity on stress tolerance in mice. METHODS: Behavioral responses to stress were assessed using the repeated social defeat stress (R-SDS) and social interaction test (SIT) model. Neurotransmitter levels in stress-related brain regions were analyzed in mice fed a solid diet (promoting masticatory activity) or a powdered diet (decreasing masticatory activity). RESULTS: Mice fed the powdered diet exhibited reduced stress tolerance compared with those fed the solid diet. Following the R-SDS, the powdered diet group displayed elevated gamma-aminobutyric acid (GABA) and norepinephrine levels in the prefrontal cortex. Before stress treatment, glutamic acid levels increased and those of choline decreased in the amygdala, whereas dopamine levels decreased in the powdered diet group after the R-SDS. In the locus coeruleus, mice on the powdered diet showed decreased glutamic acid and adenosine levels, alongside increased GABA levels. Serotonin levels decreased in the powdered diet group after the R-SDS, with no changes observed after the SIT. In the ventral hippocampus, GABA levels increased in the powdered diet group but decreased after the SIT. CONCLUSIONS: This study demonstrates a correlation between masticatory activity and stress tolerance, evidenced by both behavioral and neurotransmitter changes. These findings suggest that reduced masticatory activity due to dietary texture contributes to decreased stress resilience.