Objectives: This study aimed to investigate the age-related changes of fibroblast growth factor receptor-3 (FGFR-3) and Estrogen receptor alpha (ER-α) concentration in condyle and plasma in C5B7L male mice. Material and Methods: A total of 36 male C5B7L mice were categorized into three age groups: 28, 56, and 84 days old. The extraction of protein from condyles and the collection of plasma were conducted on the mice. The concentrations of FGFR-3 and ER in condyles and plasma were assessed using an enzyme-linked immunosorbent assay. Results: FGFR-3 levels in condyle decreased with age, while ER-α levels initially decreased at 56-day-old and then increased at 84-day-old. In plasma, the FGFR-3 level increased at 56 days and decreased at 84 days, whereas ER-α increased with age. The analysis of variance analysis of variance showed significant differences in mean values for FGFR-3 in condyle and plasma, and ER-α in plasma. Kruskal–Wallis test revealed a statistically significant difference in the ER-α mean values in the condyle (p < 0.05). Post hoc tests showed significant differences in FGFR-3 and ER-α in condyles of mice aged 28 and 56 days) and between 28 and 84 days. In plasma, the post hoc test showed a significant difference in FGFR-3 levels between ages 56 and 84 days, whereas ER-α levels showed differences between 28 and 84 days. Conclusion: FGFR-3 and ER-α levels in condyle and plasma showed different patterns as age increased. The highest concentration in the condyle was observed in 28-day-old mice, followed by a significant decline, suggesting a potential role for FGFR-3 and ER-α in regulating the terminal growth period of the mandible. © 2026 Published by Scientific Scholar on behalf of APOS Trends in Orthodontics.