Background <p>Inconsistent findings have emerged from studies examining the relationship between thyroid hormone sensitivity indices and triglycerides (TGs), especially in pediatric and adolescent cohorts. The present study investigates this relationship within adolescent populations in the United States.</p> Methods <p>Data spanning three periods from 2007 to 2012 were analyzed, including 1813 participants. The thyroid hormone sensitivity index was calculated and weighted multiple linear regression was used to assess the relationships between TG levels and individual thyroid hormone sensitivity indices. Subgroup analyses were conducted as needed and smooth curve fitting plots visualized the linear relationships.</p> Results <p>The FT3/FT4 ratio was positively correlated with TG (β = 0.649, 95% CI: 0.360–0.938, <i>P</i> &lt; 0.001). This correlation persisted after adjusting for all variables (β = 0.439, 95% CI: 0.154–0.725, <i>P</i> &lt; 0.01). The relationship between the TFQI score and TG concentration demonstrated a significant negative correlation, which remained after controlling for all covariates (β = -0.153, 95% CI: -0.239–0.067, <i>P</i> &lt; 0.01). When stratified into quartiles, the FT3/FT4 ratio and TG exhibited a positive correlation only in the Q3 and Q4 groups. Conversely, the TFQI was significantly correlated with TG exclusively in the Q4 group’s positive values. Stratified analyses by sex and age showed clearer associations in female adolescents.</p> Conclusions <p>The study confirmed the relationship between thyroid hormone sensitivity indices and TGs. Maintaining the FT3/FT4 ratio within a specific range may reduce TG levels. The TFQI may predict TG levels when actual TSH values exceed expected values based on FT4. These findings were most pronounced in female adolescents, highlighting the importance of early monitoring of thyroid health in this group. These results point to the need for improved thyroid function testing in predicting TG levels and preventing hypertriglyceridemia.</p>