Background: The role of behavioral medicine in the symptom management of glioma patients is largely unknown. Moreover, although the literature revealed that family caregivers are at risk of physical and psychological burden, the needs of caregivers generally remain unaddressed. The purpose of this study was to establish feasibility and preliminary efficacy of a couple-based Yoga (CBY) intervention in glioma patients and their caregivers targeting QOL outcomes. Methods: This small, single-arm pilot trial included adults with low and high grade glioma undergoing XRT and their family caregivers. Dyads participated in a 12-session CBY program focusing on breathing exercises, gentle movements and guided meditations. We tracked feasibility data and assessed levels of cancer-related symptoms (MDASI), depressive symptoms (CES-D), fatigue (BFI), sleep disturbances (PSQI), spiritual well-being (FACT-SP) and overall mental and physical QOL (SF-36) at baseline and post-CBY, which was at the end of XRT. Participants also completed program evaluations. Results: We approached 7 dyads of which 5 (71%) consented. All participants completed all 12 sessions and pre/post assessments. All patients (mean age: 52 yrs., 80% female, 80% high grade) and caregivers (mean age: 58 yrs., 60% female, 60% spouses) indicated that they perceived benefit from the program. Paired t-tests revealed a marginally significant, yet clinically meaningful, decrease in patient’s cancer symptoms (t = 2.32, p = .08; MDASI mean; 32.06 vs.18.80). There were clinically significant reductions in patient sleep disturbances (PSQI mean: 10.75 vs. 8.00) and improvements in patient and caregiver mental QOL (MCS of SF-36 mean: 42.35 vs 52.34 and 45.14 vs 51.43, respectively). All other means were generally in the expected direction. Conclusions: This novel supportive care program appears to be safe, feasible, acceptable, and subjectively useful for glioma patients and their caregivers. Although the trial did not have a control group, it is notable that multiple symptom outcomes improved when they would normally have been expected to deteriorate over the course of XRT. We are currently conducting a randomized controlled trial to examine treatment efficacy. Clinical trial information: 2015-01124.