Regular exercise can reduce depression. However, the uptake of exercise is limited in patients with end-stage renal disease undergoing hemodialysis. To address the gap, we designed a gamified non-weight-bearing exercise program (Exergame), which can be executed during hemodialysis treatment. The Exergame is virtually supervised based on its interactive feedback via wearable sensors attached on lower extremities. We examined the effectiveness of this program to reduce depression symptom compared to supervised exercise in 73 hemodialysis patients (age=64.5±8.7years, BMI=31.6±7.6kg/m2). Participants were randomized into an Exergame group (EG) or a Supervised-exercise group (SG). Both groups received similar exercise tasks for 4-week, 3-session per week, 30-min per session, during hemodialysis treatment. Depression symptom was assessed at baseline and 4-week using Center for Epidemiologic Studies Depression (CES-D). Both groups showed significant reduction in depression score (37%, p<0.001, Cohen’s effect size d=0.69 in EG vs. 41%, p<0.001, d=0.65 in SG) with no between-group difference for the observed effect (p>0.050). The EG expressed a positive exercise experience including fun, safety, and helpfulness of sensor-feedback. Together, results suggested that the virtually-supervised low-intensity Exergame is feasible during routine hemodialysis treatment. It is as effective as supervised-exercise to reduce depression symptom, while reducing burden of administrating exercise in dialysis clinics.