Background: Information regarding the mediation effects of thyroid function in associations between phthalates exposure and glucose metabolism including insulin resistance is unclear. Objective: Our aim was to examine whether thyroid hormone levels could mediate the associations between phthalates exposure and insulin resistance. Method: Eleven urinary phthalate metabolites levels, five thyroid hormone levels and insulin resistance (by using the Homeostatic Model Assessment of estimated Insulin Resistance [HOMA-IR]) were determined in a cross-sectional study comprised of 217 Taiwanese adults. Associations between urinary phthalate metabolite levels, serum thyroid hormone levels and HOMA-IR were explored using multiple regression models. Mediation analysis was conducted to assess the role of thyroid function in the associations between phthalates exposure and HOMA-IR. Results: Urinary mono-ethylhexyl phthalate (MEHP) levels were negatively associated with free thyroxine (free T4) (β= -0.018 ; 95% confidence interval [CI]: -0.031, -0.005 ) and positively associated with HOMA-IR (β=0.051, 95% CI: 0.012, 0.090), respectively. Urinary mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) levels were associated with free T4 (β= -0.036, 95% CI:-0.056, -0.017) and HOMA-IR (β=0.070 , 95% CI: 0.013, 0.126), respectively. Free T4 was negatively associated with HOMA-IR (β= -0.757, 95% CI:-1.122, -0.392). The results of mediation analysis indicated that 24% of the association between urinary MEHP and HOMA-IR was mediated by free T4, as well as 35% of the association between urinary MEOHP and HOMA-IR was mediated by free T4. Conclusions: Our findings support the hypothesis that thyroid function could mediate the association between phthalates exposure and glucose metabolism in adults.