Background: This prospective randomized controlled study is the first study that evaluates the disease-specific gamification through virtual reality (VR) glasses on pain, disability, functionality, and balance in knee osteoarthritis (OA). Materials and Methods: The demographic data of the patients were recorded. A total of 73 patients were divided into two groups (35 in experimental group and 38 in control group). All patients were evaluated with pain (visual analog scale [VAS]), functionality (Lysholm functional knee score [LFKS], 6 minutes walking test [6MWT]), disability (Western Ontario and McMaster Universities Arthritis Index [WOMAC]), and balance (Berg Balance Scale [BBS]) before treatment, after treatment (3th weeks), and 4 weeks after treatment (7th weeks). In the experimental group, plus the conservative treatment, a total of 15 sessions of a disease-specific gamification through VR glasses were applied. Results: VAS and WOMAC scores of the experimental group were lower at the 3th and 7th weeks than those of the control group (P = 0.005, P = 0.000), (P = 0.000). LFKS of the experimental group was higher at the 3th and 7th weeks than that of the control group (P = 0.005, P = 0.013). No difference was found between the groups in terms of 6MWTs (P > 0.05). BBS score of the experimental group was higher in the 7th week than that of the control group (P = 0.021). Conclusion: In knee OA, the disease-specific gamification through VR glasses added to the conservative treatment has a positive effect on pain, functionality, and balance. Side effects such as mild nausea, headache that did not last long, require additional treatment. In light of this, disease-specific gamification through VR glasses is effective and safe in knee OA, more studies that reveal the long-Term effect on structural healing must be planned.