Exposure to fine particulate matter (PM_2.5) is linked to metabolic dysfunction, yet evidence on its impact on hormonal regulation remains limited. This study examined seasonal changes in insulin, adiponectin, leptin, and HOMA-IR levels among healthy individuals and those with metabolic syndrome (MS) in Chiang Mai, Thailand. Fifty participants (25 healthy, 25 with MS) were assessed during high (February–April)- and low (May–July)-PM_2.5 seasons. Insulin levels increased in healthy individuals (mean: 9.3 to 14.9 µIU/mL; p = 0.051) and decreased in participants with MS (22.0 to 13.7 µIU/mL; p = 0.214), with a significant interaction effect (p = 0.020). Leptin increased significantly in both groups, but more markedly in the MS group (p < 0.001), also with a significant interaction (p < 0.001). HOMA-IR rose significantly in healthy individuals (p = 0.036) but not in participants with MS. Adiponectin remained stable across groups and seasons. At baseline, the MS group had significantly higher rates of diabetes (p = 0.050), hypertension (p = 0.001), and hyperlipidemia (p = 0.049). These findings suggest that PM_2.5 may influence metabolic and hormonal profiles, particularly in individuals with existing metabolic disorders.