Osteoarthritis is a joint degeneration and proliferative inflammatory disease caused by obesity, joint deformities, trauma, and other factors. C-terminal collagen (CTX) is associated with cartilage degradation, and healthy cartilage state is one of the factors that affect osteoarthritis. microRNA-98 (miRNA-98) plays a role in inflammation. This study aims to investigate the levels of CTX-III and miRNA-98 in patients with osteoarthritis and their potential clinical usage. Osteoarthritis was diagnosed according to the inclusion and exclusion criteria for osteoarthritis. Patients with osteoarthritis admitted to Jining No. 1 People's Hospital and healthy volunteers were included in this study. ELISA and Western blot analysis were used to detect levels of type III collagen CTX (CTX-III). Real time PCR was used to measure levels of miRNA-98 in the serum of both patients and healthy volunteers. Levels of CTX-III protein in osteoarthritis patients were significantly higher than that of healthy volunteers (p = 0.0013). Levels of miRNA-98 in the serum of osteoarthritis patients were significantly higher compared to that of healthy volunteers (p = 0.0065). After treatment, levels of CTX-III protein and serum miRNA-98 in patients with osteoarthritis were significantly decreased (p = 0.014, p = 0.021). Levels of CTX-III protein and serum miRNA-98 in patients with osteoarthritis were significantly higher compared to that of healthy volunteers (p = 0.0013). Both of the CTX-III and microRNA-98 are potential diagnostic indicators for the osteoarthritis.