This study was conducted to assess the effects of applying a gel ofcombined glucosamine sulfate and chondroitin sulfate on the temporomandibular joint (TMJ) area in patients with skeletal Class II malocclusion treated by removable functionalappliances in terms of TMJ internal proportions, levels of pain, and tension. The study included 36 patients aged 10-13 years with skeletal Class II malocclusion due to retrusion of the mandible characterized by:4-8 degrees of the sagittal skeletal discrepancy (ANB) angle,4-7 mm of overjet,72-76 degrees of the sagittal mandibular positioning (SNB) angle, and a bone maturity stage locatedat pubertal growth spurt. Patients were distributed to the experimental group (Twin-Block appliance + Jointance®gel)or thecontrol group (conventional treatment with the Twin-Block appliance). An allocation ratio of 1:1 was employed. Pre- and post-treatment digital lateral cephalometric radiograms were taken, and the TMJ joint spaces were measured using the Viewbox software (dHAL Software, Kifissia, Greece). The pain and discomfort levels were evaluated using a questionnaire with a four-point Likert scale at three assessment times. The anterior and posterior glenoid and anterior condylar distances to the pterygoid vertical (PTV) reference planesignificantly decreased after treatment (p<.001), and the anterior joint space decreased significantly (p<.001). In contrast, the superior distance of the condyle to the Frankfort horizontal reference planeincreased significantly after treatment, and the same results were found for the posterior and superior joint spaces (p<.05). There were no significant differences between the two groups in the evaluatedlinear variables. No significant differences were found when comparing pain and tension levels between the two groups at each assessment time. A gradual decrease in pain and tension levels was observed between the three evaluation times in both groups. A combinationof glucosamine sulfate and chondroitin sulfate did not affect the temporomandibular joint spaces, pain, and tension levelsin patients with skeletal Class II malocclusions treated by removable functional appliances.