Background <p>Inline speed skaters require repetitive lower-limb loading and precise ankle control, exposing athletes to instability risks. Proprioceptive-strengthening exercise is recommended to improve neuromuscular performance and reduce injury risk. Its effects on neurotrophic biomarkers, particularly irisin (primary outcome) and Brain-Derived Neurotrophic Factor (BDNF, secondary outcome), together with functional adaptations in adolescent inline speed skaters, remain insufficiently understood.</p> Methods <p>30 adolescent inline speed skaters (11–15&#xa0;years; 15 males, 15 females) were randomized into intervention (<i>n</i> = 15) and control (<i>n</i> = 15) groups. The intervention group completed an 8-week proprioceptive–strengthening program (3 sessions/week), while controls continued routine training. Primary outcome was serum irisin; secondary outcomes included BDNF, ankle stability (Single-Leg Stand), muscle strength (hamstrings, gluteus maximus, gastrocnemius), and dynamic balance (Single-Leg Squat, Overhead Squat). Assessments were performed pre- and post-intervention. Between-group changes were analyzed using 2 × 2 Mixed ANOVA (Time × Group) with baseline values as covariates, reporting F-statistics, p values, and partial η². Bonferroni correction was applied for multiple comparisons.</p> Results <p>Irisin increased significantly in the intervention group compared with the controls (Time × Group interaction: F(1, 28) = 15.42, <i>p</i> &lt; 0.001, partial <i>η</i>² = 0.355). BDNF showed a non-significant rise (F(1, 28) = 2.21, <i>p</i> = 0.110, partial <i>η</i>² = 0.073). Ankle stability improved in trunk flexion, trunk lateral flexion, pelvis tilt, and neck lateral flexion (all <i>p</i> &lt; 0.05), with between-group differences notable for trunk flexion. Muscle strength gains were consistent across all tested groups (<i>p</i> &lt; 0.05), while the controls showed no change. Dynamic balance improved in knee flexion and trunk lateral flexion, with significant between-group differences in knee flexion.</p> Conclusions <p>Eight weeks of proprioceptive-strengthening exercise enhanced irisin levels, ankle stability, muscle strength, and dynamic balance in adolescent inline speed skaters. BDNF changes were not significant, underscoring the need for cautious interpretation of biomarker outcomes. These findings provide preliminary evidence of potential benefits for youth athletic conditioning. However, given the small sample size, short duration, and lack of standardized training volume, further studies with larger cohorts and maturation control are required before extrapolation to neurorehabilitation contexts.</p> Trial registration <p>Indonesia Clinical Research Registry (INA-CRR): INA-4832FDB, Date of registration: 13th January 2026.</p>