Background: Temporomandibular disorders (TMD) may be associated with degenerative disease of temporomandibular joint (TMJ), such as condyle erosion and subchondral cysts. Occlusal splint and cranio-mandibular manual therapy, or combined therapy, is recommended as a conservative treatment to alleviate pain-related signs and symptoms in TMD. This study aimed to assess osseous condylar changes and skeletal changes following occlusal splint and cranio-mandibular manual therapy in TMD using cone beam computed tomography (CBCT). Methods: A retrospective cohort study included 24 patients diagnosed with TMD. Combined therapy was performed until pain-related signs and symptoms disappeared. CBCT scans were performed before and after therapy. Osseous structure of condyles and their subsequent modifications were analyzed on CBCT images: flattening, erosion, and subchondral cyst. Sella-Nasion-A point (SNA), Sella-Nasion-B point (SNB), A point-Nasion-B point (ANB), Sella-Articulare-Gonion (Condylar angle), and anterior and posterior facial height (AFH, PFH) were measured on CBCT-generated lateral cephalograms. A paired t-test, Wilcoxon rank-sum test, McNemar test, and Stuart-Maxwell test were used for the statistical analyses. Results: The treatment period with combined therapy was 7.42 ± 3.27 months, and 21 out of 33 TMJ presenting degenerative disease (63.6%) had significant complete remodeling (p < 0.05). Following therapy, SNB significantly decreased from 75.61 ±3.47° to 74.82 ± 3.41° (p = 0.02), ANB significantly increased from 4.05° (3.35-4.9°) to 4.8° (3.3-6.12°) (p < 0.001), AFH significantly increased from 112.85 mm (109.28-118.72) to 115.3 mm (112.58-118.88) (p < 0.001), PFH/AFH significantly decreased from 64.17 (61.39-66.1) to 63 (59.68-64.51) (p = 0.012), and condylar angle significantly increased from 140.84 ± 8.18° to 144.42 ± 8.87° (p = 0.007). Conclusion: Combined therapy promoted significant condylar remodeling in TMJ degenerative disease, along with skeletal changes (mandibular retrusion and increase in facial height). Therapeutic strategies should consider condylar remodeling in TMD. Skeletal and dental parameters should be evaluated prior to occlusal splint therapy.